Granted Patent B1

US 12,637,716 · App. 15/996,157 · Granted May 26, 2026

Inventors: Elisha Hughes (Salt Lake City, UT); Alexander Gutin (Salt Lake City, UT)

Assignee: Myriad Genetics, Inc.

C12Q1/6886C12Q1/6827G16B30/00G16H50/20G16H50/50C12Q2600/106G01N2800/52G01N2800/56G01N2800/60

Abstract

Claims (2429)

1 . A method for assessing risk for developing breast cancer comprising:

(1) obtaining genomic DNA (gDNA) from a blood, saliva, or fibroblast sample from a subject;

(2) sequencing, via targeted next generation sequencing, the gDNA to detect both the subject's genotype for a plurality of test genomic loci comprising at least 90 or more test genomic loci and a locus in linkage disequilibrium with one or more of said test genomic loci, and wherein the test genomic loci are selected from:

SNP

SNP

SNP

SNP

Designation

Designation

Designation

Designation

Panel 1

chr17:29230520:D

rs12662670

rs2236007

rs6507583

rs10069690

rs12710696

rs2363956

rs6678914

rs1011970

rs1292011

rs2380205

rs6762644

rs1045485

rs13162653

rs2588809

rs6796502

rs10472076

rs132390

rs2736108

rs6828523

rs1053338

rs13267382

rs2823093

rs6964587

rs10759243

rs13281615

rs2943559

rs704010

rs10771399

rs13329835

rs2981579

rs7072776

rs10941679

rs13365225

rs3760982

rs720475

rs10995190

rs13387042

rs3803662

rs72755295

rs11075995

rs1353747

rs3817198

rs745570

rs11199914

rs1432679

rs3903072

rs75915166

rs11242675

rs1436904

rs4245739

rs7707921

rs11249433

rs1550623

rs4593472

rs7726159

rs11552449

rs16857609

rs4808801

rs78540526

rs11571833

rs17356907

rs4849887

rs7904519

rs11621587

rs17529111

rs4973768

rs8170

rs11627032

rs17817449

rs527616

rs865686

rs11780156

rs17879961

rs554219

rs889312

rs11814448

rs186951

rs6001930

rs9257408

rs11820646

rs2012709

rs616488

rs941764

rs12048493

rs2016394

rs62070644

rs9693444

rs12405132

rs204247

rs6472903

rs9790517

rs12422552

rs2046210

rs6504950

rs999737

rs12493607

Panel 2

rs10069690

rs12710696

rs2363956

rs6507583

rs1011970

rs1292011

rs2380205

rs6678914

rs1045485

rs13162653

rs2588809

rs6762644

rs10472076

rs132390

rs2736108

rs6796502

rs1053338

rs13267382

rs2823093

rs6828523

rs10759243

rs13281615

rs2943559

rs6964587

rs10771399

rs13329835

rs2981579

rs704010

rs10941679

rs13365225

rs3760982

rs7072776

rs10995190

rs13387042

rs3803662

rs720475

rs11075995

rs1353747

rs3817198

rs72755295

rs11199914

rs1432679

rs3903072

rs745570

rs11242675

rs1436904

rs4245739

rs75915166

rs11249433

rs1550623

rs4593472

rs7707921

rs11552449

rs16857609

rs4808801

rs7726159

rs11571833

rs17356907

rs4849887

rs78540526

rs11627032

rs17529111

rs4973768

rs7904519

rs11780156

rs17817449

rs527616

rs8170

rs11814448

rs17879961

rs554219

rs865686

rs11820646

rs2012709

rs6001930

rs889312

rs12405132

rs2016394

rs616488

rs941764

rs12422552

rs204247

rs62070644

rs9693444

rs12493607

rs2046210

rs6472903

rs9790517

rs12662670

rs2236007

rs6504950

rs999737

Panel 3

rs10069690

rs13162653

rs2588809

rs6796502

rs1011970

rs132390

rs2736108

rs6828523

rs10472076

rs13267382

rs2823093

rs6964587

rs1053338

rs13281615

rs2943559

rs704010

rs10759243

rs13329835

rs2981579

rs7072776

rs10771399

rs13365225

rs3760982

rs720475

rs10941679

rs13387042

rs3803662

rs72755295

rs10995190

rs1353747

rs3817198

rs745570

rs11199914

rs1432679

rs3903072

rs75915166

rs11242675

rs1436904

rs4593472

rs7707921

rs11249433

rs1550623

rs4808801

rs7726159

rs11552449

rs16857609

rs4849887

rs78540526

rs11571833

rs17356907

rs4973768

rs7904519

rs11627032

rs17529111

rs527616

rs8170

rs11780156

rs17817449

rs554219

rs865686

rs11814448

rs17879961

rs6001930

rs889312

rs11820646

rs2012709

rs616488

rs941764

rs12405132

rs2016394

rs62070644

rs9693444

rs12493607

rs204247

rs6472903

rs9790517

rs12662670

rs2046210

rs6504950

rs999737

rs12710696

rs2236007

rs6507583

rs1292011

rs2363956

rs6762644

Panel 4

rs10069690

rs1292011

rs2236007

rs6762644

rs1011970

rs13162653

rs2588809

rs6796502

rs10472076

rs132390

rs2736108

rs6828523

rs1053338

rs13267382

rs2823093

rs6964587

rs10759243

rs13281615

rs2943559

rs704010

rs10771399

rs13329835

rs2981579

rs7072776

rs10941679

rs13365225

rs3760982

rs720475

rs10995190

rs13387042

rs3803662

rs72755295

rs11199914

rs1353747

rs3817198

rs745570

rs11242675

rs1432679

rs3903072

rs75915166

rs11249433

rs1436904

rs4593472

rs7707921

rs11552449

rs1550623

rs4808801

rs7726159

rs11571833

rs16857609

rs4849887

rs78540526

rs11627032

rs17356907

rs4973768

rs7904519

rs11780156

rs17529111

rs527616

rs865686

rs11814448

rs17817449

rs554219

rs889312

rs11820646

rs17879961

rs6001930

rs941764

rs12048493

rs2012709

rs616488

rs9693444

rs12405132

rs2016394

rs6472903

rs999737

rs12493607

rs204247

rs6504950

rs12662670

rs2046210

rs6507583

and

(3) determining or estimating the subject's risk for developing breast cancer based at least in part on the genotypes detected in (2), and a test score derived from the genotypes detected in (2), wherein calculating the test score comprises calculating, using a computer program, the following general formula: Σ (weighted genotype value for each test locus) , where the weighted genotype value for each test locus=(Coefficient)*((Genotype Value)−(Mean Allele Copy Value)).

2 . The method for assessing risk for developing breast cancer of claim 1 , further comprising

(4)(a) diagnosing a subject for whom the score in (3) exceeds a reference score as having a test likelihood of developing breast cancer that is higher than a reference likelihood of developing breast cancer, or

(4)(b) diagnosing a subject for whom the score in (3) does not exceed a reference score as having a test likelihood of developing breast cancer that is equal to or lower than a reference likelihood of developing breast cancer.

3 . The method of claim 2 , further comprising determining or estimating the subject's percent probability of developing breast cancer within one or more specific periods of time.

4 . The method of claim 3 , wherein the periods of time are chosen from the next five years; a plurality of five-, ten-, 15-, or 20-year intervals; the remainder of the subject's expected lifetime; or any time before a specific age selected from 50, 55, 60, 65, 70, 75, 80, 85, or 90 years of age.

5 . The method of claim 1 , wherein the subject does not or has been determined to not harbor a pathogenic or likely pathogenic variant in one or more genes or panel of genes selected from:

Gene

#

Panel B

Panel C

Panel D

Panel E

Panel F

Panel G

1

BRCA1

BRCA1

BRCA1

MLH1

BRCA1

BRCA1

2

BRCA2

BRCA2

BRCA2

MSH2

BRCA2

BRCA2

3

MLH1

MLH1

CHEK2

MSH6

MLH1

MLH1

4

MSH2

MSH2

ATM

PMS2

MSH2

MSH2

5

MSH6

MSH6

NBN

BRCA1

MSH6

MSH6

6

PMS2

PMS2

PALB2

BRCA2

PMS2

PMS2

7

EPCAM

EPCAM

BARD1

ATM

EPCAM

EPCAM

8

MUTYH

MUTYH

BRIP1

BARD1

APC

APC

9

APC

APC

PMS2

BRIP1

MUTYH

MUTYH

10

CDKN2A

CDKN2A

MSH2

CHEK2

PALB2

PALB2

11

PALB2

PALB2

MSH6

MUTYH

CDKN2A

CHEK2

12

SMAD4

SMAD4

TP53

RAD50

CDK4

PTEN

13

BMPR1A

BMPR1A

MUTYH

EPCAM

TP53

STK11

14

TP53

TP53

PTEN

CDH1

15

PTEN

PTEN

CDH1

TP53

16

STK11

STK11

STK11

ATM

17

CDH1

CDH1

SMAD4

RAD51C

18

NBN1

NBN1

BMPR1A

RAD51D

19

CHEK2

CHEK2

ATM

BRIP1

20

RAD51C

RAD51C

CHEK2

BARD1

21

RAD51D

RAD51D

RAD51C

BMPR1A

22

BRIP1

BRIP1

RAD51D

SMAD4

23

BARD1

BARD1

MLH3

CDKN2A

24

ATM

ATM

BRIP1

CDK4

25

CDK4

CDK4

BARD1

RAD50

26

RAD50

NSB1

NBN

27

MRE11A

RAD50

MRE11

28

MLH3

MRE11A

MLH3

29

MITF

HOXB13

30

ELAC2

Gene

#

Panel H

Panel I

Panel J

Panel K

Panel L

Panel M

Panel N

1

APC

ATM

APC

BLM

ATR

BRCA1

BRCA1

2

BRCA1

BMPR1A

ATM

CEBPA

BARD1

BRCA2

BRCA2

3

BRCA2

CDH1

BMPR1A

FLCN

BRAF

MLH1

MLH1

4

CDKN2A

CDK4

BRCA1

MEN1

BRIP1

MSH2

MSH2

5

EPCAM

CHEK2

BRCA2

PTCH

FANCA

MSH6

MSH6

6

MLH1

HOXB13

CDH1

RET

FANCB

PMS2

PMS2

7

MSH2

TP53

CDK4

SDHAF2

FANCC

EPCAM

EPCAM

8

MSH6

PTEN

CDKN2A

SDHB

FANCD2

MUTYH

MUTYH

9

MUTYH

SMAD4

CHEK2

SDHC

FANCE

APC

APC

10

PALB2

STK11

EPCAM

SDHD

FANCF

CDKN2A

CDKN2A

11

PMS2

MLH1

TMEM127

FANCG

PALB2

PALB2

12

MSH2

VHL

FANCI

SMAD4

SMAD4

13

MSH6

FANCL

BMPR1A

BMPR1A

14

MUTYH

FANCM

TP53

TP53

15

TP53

KRAS

PTEN

PTEN

16

PALB2

MLH3

STK11

STK11

17

PMS2

MRE11

CDH1

CDH1

18

PTEN

NBS1

NBN1

NBN1

19

SMAD4

PIK3CA

CHEK2

CHEK2

20

STK11

PMS1

RAD51C

RAD51C

21

RAD50

RAD51D

RAD51D

22

RAD51C

BRIP1

BRIP1

23

BARD1

BARD1

24

ATM

ATM

25

CDK4

CDK4

26

MITF

27

ELAC2

Gene

Gene

Gene

Gene

#

Symbol

Gene #

Symbol

Gene #

Symbol

1

BRCA1

24

PALB2

47

RAD50

2

BRCA2

25

TP53

48

MRE11

3

MLH1

26

FANCL

49

BRIP1

4

MSH2

27

BLM

50

FLCN

5

PMS2

28

CDK4

51

TMEM127

6

MLH3

29

CDKN2A

52

PIK3CA

7

EPCAM

30

ATM

53

KRAS

8

MSH6

31

PTCH1

54

BRAF

9

APC

32

CHEK2

55

HOXB13

10

PMS1

33

RAD51C

56

ATR

11

PTEN

34

CEBPA

57

BAP1

12

STK11

35

NBS1

58

CFTR

13

RET

36

FANCA

59

CTRC

14

SDHD

37

FANCC

60

FGFR2

15

SDHC

38

FANCD2

61

FH

16

SDHB

39

FANCE

62

HRAS

17

SDHAF2

40

FANCG

63

KITLG

18

CDH1

41

FANCI

64

NF1

19

MUTYH

42

FANCM

65

NF2

20

SMAD4

43

RAD51D

66

PRSS1

21

MEN1

44

FANCF

67

RB1

22

VHL

45

FANCB

68

SPINK1

23

BMPR1A

46

BARD1

69

TGFB2

Gene

Gene

Gene

Gene

#

Symbol

Gene #

Symbol

Gene #

Symbol

1

BRCA1

24

VHL

47

NBS1

2

BRCA2

25

MEN1

48

RAD50

3

MLH1

26

RET

49

FANCA

4

MSH2

27

NF1

50

FANCB

5

MSH6

28

NF2

51

FANCC

6

PMS2

29

RB1

52

FANCD2

7

EPCAM

30

PTCH1

53

FANCE

8

APC

31

FH

54

FANCF

9

MUTYH

32

BLM

55

FANCG

10

PALB2

33

CEBPA

56

FANCI

11

CDKN2A

34

FLCN

57

FANCL

12

CDK4

35

SDHB

58

FANCM

13

TP53

36

SDHC

59

ATR

14

PTEN

37

SDHD

60

HRAS

15

CDH1

38

SDHAF2

61

TGFB2

16

STK11

39

TMEM127

62

FGFR2

17

SMAD4

40

CFTR

63

BAP1

18

BMPR1A

41

PRSS1

64

KITLG

19

ATM

42

CTRC

65

BRAF

20

CHEK2

43

SPINK1

66

MRE11

21

RAD51C

44

KRAS

67

PIK3CA

22

RAD51D

45

BRIP1

68

PMS1

23

MLH3

46

BARD1

69

HOXB13

6 . The method of claim 5 , wherein the plurality of test genes comprise: APC, ATM, BAP1, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A, CHEK2, EPCAM, FH, FLCN, HOXB13, MEN1, MITF, MLH1, MSH2, MSH6, MUTYH, PALB2, PMS2, PTEN, RAD51C, RAD51D, RET, SDHB, SDHC, SDHD, SMAD4, STK11, TP53, and VHL.

7 . The method of claim 1 , wherein determining in (3) comprises determining or estimating the subject's percent probability of developing breast cancer within one or more specific periods of time.

8 . The method of claim 7 , wherein the periods of time are chosen from the next five years; a plurality of five-, ten-, 15-, or 20-year intervals; the remainder of the subject's expected lifetime; or any time before a specific age selected from 50, 55, 60, 65, 70, 75, 80, 85, or 90 years of age.

9 . The method of claim 1 , wherein determining in (3) comprises determining the subject's risk for developing breast cancer attributable or allocable to the genotypes detected in (2) in combination with other risk factors or calculations to yield a composite risk score or estimation.

10 . The method of claim 1 , wherein the subject has a significant family history of breast cancer and tested negative for known high and intermediate risk mutations.

11 . The method of claim 1 , further comprising outputting the risk of the subject for developing breast cancer.

12 . The method of claim 1 , wherein the test genomic loci comprise: rs616488, rs11552449, rs11249433, rs12405132, rs6678914, rs4245739, rs72755295, rs12710696, rs4849887, rs2016394, rs1550623, rs1045485, rs13387042, rs16857609, rs6762644, rs4973768, rs12493607, rs6796502, rs1053338, rs9790517, rs6828523, rs10069690, rs7726159, rs2736108, rs13162653, rs2012709, rs10941679, rs889312, rs10472076, rs1353747, rs7707921, rs1432679, rs11242675, rs204247, rs17529111, rs12662670, rs2046210, rs6964587, rs4593472, rs720475, rs9693444, rs13365225, rs6472903, rs2943559, rs13267382, rs13281615, rs11780156, rs1011970, rs10759243, rs865686, rs2380205, rs7072776, rs11814448, rs10995190, rs704010, rs7904519, rs11199914, rs2981579, rs3817198, rs3903072, rs78540526, rs554219, rs75915166, rs11820646, rs12422552, rs10771399, rs17356907, rs1292011, rs11571833, rs2236007, rs2588809, rs999737, rs941764, rs11627032, rs3803662, rs17817449, rs11075995, rs13329835, rs6504950, rs745570, rs527616, rs1436904, rs6507583, rs8170, rs2363956, rs4808801, rs3760982, rs2823093, rs17879961, rs132390, and rs6001930.

13 . A method for assessing risk for developing breast cancer comprising:

(1) obtaining genomic DNA (gDNA) from a blood, saliva, or fibroblast sample from a subject;

(2) sequencing, via next generation sequencing, the gDNA to detect the sequence for a plurality of test genes comprising at least 30 or more genes or any panel of genes selected from:

Gene

#

Panel B

Panel C

Panel D

Panel E

Panel F

Panel G

1

BRCA1

BRCA1

BRCA1

MLH1

BRCA1

BRCA1

2

BRCA2

BRCA2

BRCA2

MSH2

BRCA2

BRCA2

3

MLH1

MLH1

CHEK2

MSH6

MLH1

MLH1

4

MSH2

MSH2

ATM

PMS2

MSH2

MSH2

5

MSH6

MSH6

NBN

BRCA1

MSH6

MSH6

6

PMS2

PMS2

PALB2

BRCA2

PMS2

PMS2

7

EPCAM

EPCAM

BARD1

ATM

EPCAM

EPCAM

8

MUTYH

MUTYH

BRIP1

BARD1

APC

APC

9

APC

APC

PMS2

BRIP1

MUTYH

MUTYH

10

CDKN2A

CDKN2A

MSH2

CHEK2

PALB2

PALB2

11

PALB2

PALB2

MSH6

MUTYH

CDKN2A

CHEK2

12

SMAD4

SMAD4

TP53

RAD50

CDK4

PTEN

13

BMPR1A

BMPR1A

MUTYH

EPCAM

TP53

STK11

14

TP53

TP53

PTEN

CDH1

15

PTEN

PTEN

CDH1

TP53

16

STK11

STK11

STK11

ATM

17

CDH1

CDH1

SMAD4

RAD51C

18

NBN1

NBN1

BMPR1A

RAD51D

19

CHEK2

CHEK2

ATM

BRIP1

20

RAD51C

RAD51C

CHEK2

BARD1

21

RAD51D

RAD51D

RAD51C

BMPR1A

22

BRIP1

BRIP1

RAD51D

SMAD4

23

BARD1

BARD1

MLH3

CDKN2A

24

ATM

ATM

BRIP1

CDK4

25

CDK4

CDK4

BARD1

RAD50

26

RAD50

NSB1

NBN

27

MRE11A

RAD50

MRE11

28

MLH3

MRE11A

MLH3

29

MITF

HOXB13

30

ELAC2

Gene

#

Panel H

Panel I

Panel J

Panel K

Panel L

Panel M

Panel N

1

APC

ATM

APC

BLM

ATR

BRCA1

BRCA1

2

BRCA1

BMPR1A

ATM

CEBPA

BARD1

BRCA2

BRCA2

3

BRCA2

CDH1

BMPR1A

FLCN

BRAF

MLH1

MLH1

4

CDKN2A

CDK4

BRCA1

MEN1

BRIP1

MSH2

MSH2

5

EPCAM

CHEK2

BRCA2

PTCH

FANCA

MSH6

MSH6

6

MLH1

HOXB13

CDH1

RET

FANCB

PMS2

PMS2

7

MSH2

TP53

CDK4

SDHAF2

FANCC

EPCAM

EPCAM

8

MSH6

PTEN

CDKN2A

SDHB

FANCD2

MUTYH

MUTYH

9

MUTYH

SMAD4

CHEK2

SDHC

FANCE

APC

APC

10

PALB2

STK11

EPCAM

SDHD

FANCF

CDKN2A

CDKN2A

11

PMS2

MLH1

TMEM127

FANCG

PALB2

PALB2

12

MSH2

VHL

FANCI

SMAD4

SMAD4

13

MSH6

FANCL

BMPR1A

BMPR1A

14

MUTYH

FANCM

TP53

TP53

15

TP53

KRAS

PTEN

PTEN

16

PALB2

MLH3

STK11

STK11

17

PMS2

MRE11

CDH1

CDH1

18

PTEN

NBS1

NBN1

NBN1

19

SMAD4

PIK3CA

CHEK2

CHEK2

20

STK11

PMS1

RAD51C

RAD51C

21

RAD50

RAD51D

RAD51D

22

RAD51C

BRIP1

BRIP1

23

BARD1

BARD1

24

ATM

ATM

25

CDK4

CDK4

26

MITF

27

ELAC2

Gene

Gene

Gene

Gene

#

Symbol

Gene #

Symbol

Gene #

Symbol

1

BRCA1

24

PALB2

47

RAD50

2

BRCA2

25

TP53

48

MRE11

3

MLH1

26

FANCL

49

BRIP1

4

MSH2

27

BLM

50

FLCN

5

PMS2

28

CDK4

51

TMEM127

6

MLH3

29

CDKN2A

52

PIK3CA

7

EPCAM

30

ATM

53

KRAS

8

MSH6

31

PTCH1

54

BRAF

9

APC

32

CHEK2

55

HOXB13

10

PMS1

33

RAD51C

56

ATR

11

PTEN

34

CEBPA

57

BAP1

12

STK11

35

NBS1

58

CFTR

13

RET

36

FANCA

59

CTRC

14

SDHD

37

FANCC

60

FGFR2

15

SDHC

38

FANCD2

61

FH

16

SDHB

39

FANCE

62

HRAS

17

SDHAF2

40

FANCG

63

KITLG

18

CDH1

41

FANCI

64

NF1

19

MUTYH

42

FANCM

65

NF2

20

SMAD4

43

RAD51D

66

PRSS1

21

MEN1

44

FANCF

67

RB1

22

VHL

45

FANCB

68

SPINK1

23

BMPR1A

46

BARD1

69

TGFB2

Gene

Gene

Gene

Gene

#

Symbol

Gene #

Symbol

Gene #

Symbol

1

BRCA1

24

VHL

47

NBS1

2

BRCA2

25

MEN1

48

RAD50

3

MLH1

26

RET

49

FANCA

4

MSH2

27

NF1

50

FANCB

5

MSH6

28

NF2

51

FANCC

6

PMS2

29

RB1

52

FANCD2

7

EPCAM

30

PTCH1

53

FANCE

8

APC

31

FH

54

FANCF

9

MUTYH

32

BLM

55

FANCG

10

PALB2

33

CEBPA

56

FANCI

11

CDKN2A

34

FLCN

57

FANCL

12

CDK4

35

SDHB

58

FANCM

13

TP53

36

SDHC

59

ATR

14

PTEN

37

SDHD

60

HRAS

15

CDH1

38

SDHAF2

61

TGFB2

16

STK11

39

TMEM127

62

FGFR2

17

SMAD4

40

CFTR

63

BAP1

18

BMPR1A

41

PRSS1

64

KITLG

19

ATM

42

CTRC

65

BRAF

20

CHEK2

43

SPINK1

66

MRE11

21

RAD51C

44

KRAS

67

PIK3CA

22

RAD51D

45

BRIP1

68

PMS1

23

MLH3

46

BARD1

69

HOXB13

(3) targeted next generation sequencing either the gDNA or a gDNA obtained or derived from a second blood, saliva, or fibroblast sample from the subject and genotyping (i) a plurality of test genomic loci comprising at least 90 or more test genomic loci wherein the test genomic loci comprise a Single Nucleotide Polymorphism (SNP), and (ii) one or more loci in linkage disequilibrium with a SNP, wherein the test genomic loci are selected from:

SNP

SNP

SNP

SNP

Designation

Designation

Designation

Designation

Panel 1

chr17:29230520:D

rs12662670

rs2236007

rs6507583

rs10069690

rs12710696

rs2363956

rs6678914

rs1011970

rs1292011

rs2380205

rs6762644

rs1045485

rs13162653

rs2588809

rs6796502

rs10472076

rs132390

rs2736108

rs6828523

rs1053338

rs13267382

rs2823093

rs6964587

rs10759243

rs13281615

rs2943559

rs704010

rs10771399

rs13329835

rs2981579

rs7072776

rs10941679

rs13365225

rs3760982

rs720475

rs10995190

rs13387042

rs3803662

rs72755295

rs11075995

rs1353747

rs3817198

rs745570

rs11199914

rs1432679

rs3903072

rs75915166

rs11242675

rs1436904

rs4245739

rs7707921

rs11249433

rs1550623

rs4593472

rs7726159

rs11552449

rs16857609

rs4808801

rs78540526

rs11571833

rs17356907

rs4849887

rs7904519

rs11621587

rs17529111

rs4973768

rs8170

rs11627032

rs17817449

rs527616

rs865686

rs11780156

rs17879961

rs554219

rs889312

rs11814448

rs186951

rs6001930

rs9257408

rs11820646

rs2012709

rs616488

rs941764

rs12048493

rs2016394

rs62070644

rs9693444

rs12405132

rs204247

rs6472903

rs9790517

rs12422552

rs2046210

rs6504950

rs999737

rs12493607

Panel 2

rs10069690

rs12710696

rs2363956

rs6507583

rs1011970

rs1292011

rs2380205

rs6678914

rs1045485

rs13162653

rs2588809

rs6762644

rs10472076

rs132390

rs2736108

rs6796502

rs1053338

rs13267382

rs2823093

rs6828523

rs10759243

rs13281615

rs2943559

rs6964587

rs10771399

rs13329835

rs2981579

rs704010

rs10941679

rs13365225

rs3760982

rs7072776

rs10995190

rs13387042

rs3803662

rs720475

rs11075995

rs1353747

rs3817198

rs72755295

rs11199914

rs1432679

rs3903072

rs745570

rs11242675

rs1436904

rs4245739

rs75915166

rs11249433

rs1550623

rs4593472

rs7707921

rs11552449

rs16857609

rs4808801

rs7726159

rs11571833

rs17356907

rs4849887

rs78540526

rs11627032

rs17529111

rs4973768

rs7904519

rs11780156

rs17817449

rs527616

rs8170

rs11814448

rs17879961

rs554219

rs865686

rs11820646

rs2012709

rs6001930

rs889312

rs12405132

rs2016394

rs616488

rs941764

rs12422552

rs204247

rs62070644

rs9693444

rs12493607

rs2046210

rs6472903

rs9790517

rs12662670

rs2236007

rs6504950

rs999737

Panel 3

rs10069690

rs13162653

rs2588809

rs6796502

rs1011970

rs132390

rs2736108

rs6828523

rs10472076

rs13267382

rs2823093

rs6964587

rs1053338

rs13281615

rs2943559

rs704010

rs10759243

rs13329835

rs2981579

rs7072776

rs10771399

rs13365225

rs3760982

rs720475

rs10941679

rs13387042

rs3803662

rs72755295

rs10995190

rs1353747

rs3817198

rs745570

rs11199914

rs1432679

rs3903072

rs75915166

rs11242675

rs1436904

rs4593472

rs7707921

rs11249433

rs1550623

rs4808801

rs7726159

rs11552449

rs16857609

rs4849887

rs78540526

rs11571833

rs17356907

rs4973768

rs7904519

rs11627032

rs17529111

rs527616

rs8170

rs11780156

rs17817449

rs554219

rs865686

rs11814448

rs17879961

rs6001930

rs889312

rs11820646

rs2012709

rs616488

rs941764

rs12405132

rs2016394

rs62070644

rs9693444

rs12493607

rs204247

rs6472903

rs9790517

rs12662670

rs2046210

rs6504950

rs999737

rs12710696

rs2236007

rs6507583

rs1292011

rs2363956

rs6762644

Panel 4

rs10069690

rs1292011

rs2236007

rs6762644

rs1011970

rs13162653

rs2588809

rs6796502

rs10472076

rs132390

rs2736108

rs6828523

rs1053338

rs13267382

rs2823093

rs6964587

rs10759243

rs13281615

rs2943559

rs704010

rs10771399

rs13329835

rs2981579

rs7072776

rs10941679

rs13365225

rs3760982

rs720475

rs10995190

rs13387042

rs3803662

rs72755295

rs11199914

rs1353747

rs3817198

rs745570

rs11242675

rs1432679

rs3903072

rs75915166

rs11249433

rs1436904

rs4593472

rs7707921

rs11552449

rs1550623

rs4808801

rs7726159

rs11571833

rs16857609

rs4849887

rs78540526

rs11627032

rs17356907

rs4973768

rs7904519

rs11780156

rs17529111

rs527616

rs865686

rs11814448

rs17817449

rs554219

rs889312

rs11820646

rs17879961

rs6001930

rs941764

rs12048493

rs2012709

rs616488

rs9693444

rs12405132

rs2016394

rs6472903

rs999737

rs12493607

rs204247

rs6504950

rs12662670

rs2046210

rs6507583

(4) calculating a test score incorporating or derived from the genotypes detected in (3), wherein calculating the test score comprises calculating, using a computer program, the following general formula: Σ (weighted genotype value for each test locus) , where the weighted genotype value for each test locus=(Coefficient)*((Genotype Value)−(Mean Allele Copy Value)); and

(5)(a) diagnosing a subject for whom the score in (4) exceeds a reference score as having a test likelihood of developing breast cancer that is higher than a reference likelihood of developing breast cancer, or

(5)(b) diagnosing a subject for whom the score in (4) does not exceed a reference score as having a test likelihood of developing breast cancer that is equal to or lower than a reference likelihood of developing breast cancer.

14 . The method of claim 13 , further comprising determining or estimating the subject's percent probability of developing breast cancer within one or more specific periods of time.

15 . The method of claim 14 , wherein the periods of time are chosen from the next five years; a plurality of five-, ten-, 15-, or 20-year intervals; the remainder of the subject's expected lifetime; or any time before a specific age selected from 50, 55, 60, 65, 70, 75, 80, 85, or 90 years of age.

16 . The method of claim 14 , wherein the percent probability of developing breast cancer is calculated according to Formula (I): Test score=1−(1−[Clinical Score]) exp(C1*[Test Score]) , or Formula (II): Test score=1−(1−[Clinical Score]) (exp(C1*[Test Score]+C2)) .

17 . The method of claim 13 , further comprising determining the subject's risk for developing breast cancer attributable or allocable to the genotypes detected in (3) in combination with other risk factors or calculations to yield a composite risk score or estimation.

18 . The method of claim 13 , further comprising outputting the risk of the subject for developing breast cancer.

19 . The method of claim 13 , wherein the test genomic loci comprise: rs616488, rs11552449, rs11249433, rs12405132, rs6678914, rs4245739, rs72755295, rs12710696, rs4849887, rs2016394, rs1550623, rs1045485, rs13387042, rs16857609, rs6762644, rs4973768, rs12493607, rs6796502, rs1053338, rs9790517, rs6828523, rs10069690, rs7726159, rs2736108, rs13162653, rs2012709, rs10941679, rs889312, rs10472076, rs1353747, rs7707921, rs1432679, rs11242675, rs204247, rs17529111, rs12662670, rs2046210, rs6964587, rs4593472, rs720475, rs9693444, rs13365225, rs6472903, rs2943559, rs13267382, rs13281615, rs11780156, rs1011970, rs10759243, rs865686, rs2380205, rs7072776, rs11814448, rs10995190, rs704010, rs7904519, rs11199914, rs2981579, rs3817198, rs3903072, rs78540526, rs554219, rs75915166, rs11820646, rs12422552, rs10771399, rs17356907, rs1292011, rs11571833, rs2236007, rs2588809, rs999737, rs941764, rs11627032, rs3803662, rs17817449, rs11075995, rs13329835, rs6504950, rs745570, rs527616, rs1436904, rs6507583, rs8170, rs2363956, rs4808801, rs3760982, rs2823093, rs17879961, rs132390, and rs6001930.

20 . The method of claim 13 , wherein the plurality of test genes comprise: APC, ATM, BAP1, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A, CHEK2, EPCAM, FH, FLCN, HOXB13, MEN1, MITF, MLH1, MSH2, MSH6, MUTYH, PALB2, PMS2, PTEN, RAD51C, RAD51D, RET, SDHB, SDHC, SDHD, SMAD4, STK11, TP53, and VHL.

21 . A method of calculating a test score comprising:

(1) targeted next generation sequencing genomic DNA (gDNA) obtained or derived from a blood, saliva, or fibroblast sample from a subject to detect both the subject's genotype for a plurality of test genomic loci comprising at least 90 or more test genomic loci and a locus in linkage disequilibrium with one or more of said test genomic loci, and wherein the test genomic loci are selected from:

SNP

SNP

SNP

SNP

Designation

Designation

Designation

Designation

Panel 1

chr17:29230520:D

rs12662670

rs2236007

rs6507583

rs10069690

rs12710696

rs2363956

rs6678914

rs1011970

rs1292011

rs2380205

rs6762644

rs1045485

rs13162653

rs2588809

rs6796502

rs10472076

rs132390

rs2736108

rs6828523

rs1053338

rs13267382

rs2823093

rs6964587

rs10759243

rs13281615

rs2943559

rs704010

rs10771399

rs13329835

rs2981579

rs7072776

rs10941679

rs13365225

rs3760982

rs720475

rs10995190

rs13387042

rs3803662

rs72755295

rs11075995

rs1353747

rs3817198

rs745570

rs11199914

rs1432679

rs3903072

rs75915166

rs11242675

rs1436904

rs4245739

rs7707921

rs11249433

rs1550623

rs4593472

rs7726159

rs11552449

rs16857609

rs4808801

rs78540526

rs11571833

rs17356907

rs4849887

rs7904519

rs11621587

rs17529111

rs4973768

rs8170

rs11627032

rs17817449

rs527616

rs865686

rs11780156

rs17879961

rs554219

rs889312

rs11814448

rs186951

rs6001930

rs9257408

rs11820646

rs2012709

rs616488

rs941764

rs12048493

rs2016394

rs62070644

rs9693444

rs12405132

rs204247

rs6472903

rs9790517

rs12422552

rs2046210

rs6504950

rs999737

rs12493607

Panel 2

rs10069690

rs12710696

rs2363956

rs6507583

rs1011970

rs1292011

rs2380205

rs6678914

rs1045485

rs13162653

rs2588809

rs6762644

rs10472076

rs132390

rs2736108

rs6796502

rs1053338

rs13267382

rs2823093

rs6828523

rs10759243

rs13281615

rs2943559

rs6964587

rs10771399

rs13329835

rs2981579

rs704010

rs10941679

rs13365225

rs3760982

rs7072776

rs10995190

rs13387042

rs3803662

rs720475

rs11075995

rs1353747

rs3817198

rs72755295

rs11199914

rs1432679

rs3903072

rs745570

rs11242675

rs1436904

rs4245739

rs75915166

rs11249433

rs1550623

rs4593472

rs7707921

rs11552449

rs16857609

rs4808801

rs7726159

rs11571833

rs17356907

rs4849887

rs78540526

rs11627032

rs17529111

rs4973768

rs7904519

rs11780156

rs17817449

rs527616

rs8170

rs11814448

rs17879961

rs554219

rs865686

rs11820646

rs2012709

rs6001930

rs889312

rs12405132

rs2016394

rs616488

rs941764

rs12422552

rs204247

rs62070644

rs9693444

rs12493607

rs2046210

rs6472903

rs9790517

rs12662670

rs2236007

rs6504950

rs999737

Panel 3

rs10069690

rs13162653

rs2588809

rs6796502

rs1011970

rs132390

rs2736108

rs6828523

rs10472076

rs13267382

rs2823093

rs6964587

rs1053338

rs13281615

rs2943559

rs704010

rs10759243

rs13329835

rs2981579

rs7072776

rs10771399

rs13365225

rs3760982

rs720475

rs10941679

rs13387042

rs3803662

rs72755295

rs10995190

rs1353747

rs3817198

rs745570

rs11199914

rs1432679

rs3903072

rs75915166

rs11242675

rs1436904

rs4593472

rs7707921

rs11249433

rs1550623

rs4808801

rs7726159

rs11552449

rs16857609

rs4849887

rs78540526

rs11571833

rs17356907

rs4973768

rs7904519

rs11627032

rs17529111

rs527616

rs8170

rs11780156

rs17817449

rs554219

rs865686

rs11814448

rs17879961

rs6001930

rs889312

rs11820646

rs2012709

rs616488

rs941764

rs12405132

rs2016394

rs62070644

rs9693444

rs12493607

rs204247

rs6472903

rs9790517

rs12662670

rs2046210

rs6504950

rs999737

rs12710696

rs2236007

rs6507583

rs1292011

rs2363956

rs6762644

Panel 4

rs10069690

rs1292011

rs2236007

rs6762644

rs1011970

rs13162653

rs2588809

rs6796502

rs10472076

rs132390

rs2736108

rs6828523

rs1053338

rs13267382

rs2823093

rs6964587

rs10759243

rs13281615

rs2943559

rs704010

rs10771399

rs13329835

rs2981579

rs7072776

rs10941679

rs13365225

rs3760982

rs720475

rs10995190

rs13387042

rs3803662

rs72755295

rs11199914

rs1353747

rs3817198

rs745570

rs11242675

rs1432679

rs3903072

rs75915166

rs11249433

rs1436904

rs4593472

rs7707921

rs11552449

rs1550623

rs4808801

rs7726159

rs11571833

rs16857609

rs4849887

rs78540526

rs11627032

rs17356907

rs4973768

rs7904519

rs11780156

rs17529111

rs527616

rs865686

rs11814448

rs17817449

rs554219

rs889312

rs11820646

rs17879961

rs6001930

rs941764

rs12048493

rs2012709

rs616488

rs9693444

rs12405132

rs2016394

rs6472903

rs999737

rs12493607

rs204247

rs6504950

rs12662670

rs2046210

rs6507583

(2) determining or estimating the subject's risk for developing breast cancer based at least in part on the genotypes detected in (1), and a test score derived from the genotypes detected in (1), wherein calculating the test score comprises calculating, using a computer program, the following general formula: Σ (weighted genotype value for each test locus) , where weighted genotype value for each test locus=(Coefficient)*((Genotype Value)−(Mean Allele Copy Value)).

22 . The method of claim 21 , further comprising outputting the risk of the subject for developing breast cancer.

23 . The method of claim 21 , wherein the test genomic loci comprise: rs616488, rs11552449, rs11249433, rs12405132, rs6678914, rs4245739, rs72755295, rs12710696, rs4849887, rs2016394, rs1550623, rs1045485, rs13387042, rs16857609, rs6762644, rs4973768, rs12493607, rs6796502, rs1053338, rs9790517, rs6828523, rs10069690, rs7726159, rs2736108, rs13162653, rs2012709, rs10941679, rs889312, rs10472076, rs1353747, rs7707921, rs1432679, rs11242675, rs204247, rs17529111, rs12662670, rs2046210, rs6964587, rs4593472, rs720475, rs9693444, rs13365225, rs6472903, rs2943559, rs13267382, rs13281615, rs11780156, rs1011970, rs10759243, rs865686, rs2380205, rs7072776, rs11814448, rs10995190, rs704010, rs7904519, rs11199914, rs2981579, rs3817198, rs3903072, rs78540526, rs554219, rs75915166, rs11820646, rs12422552, rs10771399, rs17356907, rs1292011, rs11571833, rs2236007, rs2588809, rs999737, rs941764, rs11627032, rs3803662, rs17817449, rs11075995, rs13329835, rs6504950, rs745570, rs527616, rs1436904, rs6507583, rs8170, rs2363956, rs4808801, rs3760982, rs2823093, rs17879961, rs132390, and rs6001930.

24 . A method for assessing risk for developing breast cancer of a subject comprising:

(1) obtaining genomic DNA (gDNA) obtained or derived from a blood, saliva, or fibroblast sample from a subject;

(2) sequencing, via next generation sequencing, the gDNA to detect the sequence for a plurality of test genes comprising at least 30 or more genes, wherein the plurality of test genes comprise: APC, ATM, BAP1, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A, CHEK2, EPCAM, FH, FLCN, HOXB13, MEN1, MITF, MLH1, MSH2, MSH6, MUTYH, PALB2, PMS2, PTEN, RAD51C, RAD51D, RET, SDHB, SDHC, SDHD, SMAD4, STK11, TP53, and VHL;

(3) targeted next generation sequencing either the gDNA or gDNA obtained or derived from a second blood, saliva, or fibroblast sample from the subject and genotyping (i) a plurality of test genomic loci comprising at least 90 or more test genomic loci wherein the test genomic loci comprise a SNP, and (ii) one or more loci in linkage disequilibrium with a SNP, wherein the test genomic loci comprise: rs616488, rs11552449, rs11249433, rs12405132, rs6678914, rs4245739, rs72755295, rs12710696, rs4849887, rs2016394, rs1550623, rs1045485, rs13387042, rs16857609, rs6762644, rs4973768, rs12493607, rs6796502, rs1053338, rs9790517, rs6828523, rs10069690, rs7726159, rs2736108, rs13162653, rs2012709, rs10941679, rs889312, rs10472076, rs1353747, rs7707921, rs1432679, rs11242675, rs204247, rs17529111, rs12662670, rs2046210, rs6964587, rs4593472, rs720475, rs9693444, rs13365225, rs6472903, rs2943559, rs13267382, rs13281615, rs11780156, rs1011970, rs10759243, rs865686, rs2380205, rs7072776, rs11814448, rs10995190, rs704010, rs7904519, rs11199914, rs2981579, rs3817198, rs3903072, rs78540526, rs554219, rs75915166, rs11820646, rs12422552, rs10771399, rs17356907, rs1292011, rs11571833, rs2236007, rs2588809, rs999737, rs941764, rs11627032, rs3803662, rs17817449, rs11075995, rs13329835, rs6504950, rs745570, rs527616, rs1436904, rs6507583, rs8170, rs2363956, rs4808801, rs3760982, rs2823093, rs17879961, rs132390, and rs6001930;

(4) calculating a test score incorporating or derived from the genotypes detected in (3), wherein calculating the test score comprises calculating, using the a computer program, the following general formula: Σ (weighted genotype value for each test locus) , where the weighted genotype value for each test locus=(Coefficient)*((Genotype Value)−(Mean Allele Copy Value)); and

(5)(a) diagnosing a subject for whom the score in (4) exceeds a reference score as having a test likelihood of developing breast cancer that is higher than a reference likelihood of developing breast cancer; or

(5)(b) diagnosing a subject for whom the score in (4) does not exceed a reference score as having a test likelihood of developing breast cancer that is equal to or lower than a reference likelihood of developing breast cancer.

25 . A method for genotyping a subject determined to have a risk for developing breast cancer, comprising:

(1) sequencing a gDNA from a blood, saliva, or fibroblast sample from the subject for a plurality of test genes comprising 30-50 genes, wherein the plurality of test genes comprises: APC, ATM, BAP1, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A, CHEK2, EPCAM, FH, FLCN, HOXB13, MEN1, MITF, MLH1, MSH2, MSH6, MUTYH, PALB2, PMS2, PTEN, RAD51C, RAD51D, RET, SDHB, SDHC, SDHD, SMAD4, STK11, TP53, and VHL; and

(2) targeted sequencing either the gDNA or gDNA from a second blood, saliva, or fibroblast sample from the subject and genotyping (i) a plurality of test genomic loci comprising 90-150 test genomic loci, wherein the test genomic loci comprise a SNP or (ii) one or more loci in linkage disequilibrium with the test genomic loci, wherein the test genomic loci comprise: rs616488, rs11552449, rs11249433, rs12405132, rs6678914, rs4245739, rs72755295, rs12710696, rs4849887, rs2016394, rs1550623, rs1045485, rs13387042, rs16857609, rs6762644, rs4973768, rs12493607, rs6796502, rs1053338, rs9790517, rs6828523, rs10069690, rs7726159, rs2736108, rs13162653, rs2012709, rs10941679, rs889312, rs10472076, rs1353747, rs7707921, rs1432679, rs11242675, rs204247, rs17529111, rs12662670, rs2046210, rs6964587, rs4593472, rs720475, rs9693444, rs13365225, rs6472903, rs2943559, rs13267382, rs13281615, rs11780156, rs1011970, rs10759243, rs865686, rs2380205, rs7072776, rs11814448, rs10995190, rs704010, rs7904519, rs11199914, rs2981579, rs3817198, rs3903072, rs78540526, rs554219, rs75915166, rs11820646, rs12422552, rs10771399, rs17356907, rs1292011, rs11571833, rs2236007, rs2588809, rs999737, rs941764, rs11627032, rs3803662, rs17817449, rs11075995, rs13329835, rs6504950, rs745570, rs527616, rs1436904, rs6507583, rs8170, rs2363956, rs4808801, rs3760982, rs2823093, rs17879961, rs132390, and rs6001930;

thereby providing a genotype for each of the test genes and test genomic loci.

26 . A method of sequencing genomic DNA (gDNA) from a sample, comprising:

(1) sequencing a gDNA from a blood, saliva, or fibroblast sample for a plurality of test genes comprising 30-50 genes, wherein the plurality of test genes comprises: APC, ATM, BAP1, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A, CHEK2, EPCAM, FH, FLCN, HOXB13, MEN1, MITF, MLH1, MSH2, MSH6, MUTYH, PALB2, PMS2, PTEN, RAD51C, RAD51D, RET, SDHB, SDHC, SDHD, SMAD4, STK11, TP53, and VHL; and

(2) targeted sequencing the gDNA for (i) a plurality of test genomic loci comprising 90-150 test genomic loci, wherein the test genomic loci comprise a SNP or (ii) one or more loci in linkage disequilibrium with the test genomic loci, wherein the test genomic loci comprise: rs616488, rs11552449, rs11249433, rs12405132, rs6678914, rs4245739, rs72755295, rs12710696, rs4849887, rs2016394, rs1550623, rs1045485, rs13387042, rs16857609, rs6762644, rs4973768, rs12493607, rs6796502, rs1053338, rs9790517, rs6828523, rs10069690, rs7726159, rs2736108, rs13162653, rs2012709, rs10941679, rs889312, rs10472076, rs1353747, rs7707921, rs1432679, rs11242675, rs204247, rs17529111, rs12662670, rs2046210, rs6964587, rs4593472, rs720475, rs9693444, rs13365225, rs6472903, rs2943559, rs13267382, rs13281615, rs11780156, rs1011970, rs10759243, rs865686, rs2380205, rs7072776, rs11814448, rs10995190, rs704010, rs7904519, rs11199914, rs2981579, rs3817198, rs3903072, rs78540526, rs554219, rs75915166, rs11820646, rs12422552, rs10771399, rs17356907, rs1292011, rs11571833, rs2236007, rs2588809, rs999737, rs941764, rs11627032, rs3803662, rs17817449, rs11075995, rs13329835, rs6504950, rs745570, rs527616, rs1436904, rs6507583, rs8170, rs2363956, rs4808801, rs3760982, rs2823093, rs17879961, rs132390, and rs6001930;

wherein blood, saliva, or fibroblast sample is obtained from a subject suspected to be at risk of developing breast cancer.

Assignments (3)

Continuity (3)

References Cited (79)