IP Library › Granted Patent US 12,577,622
Granted Patent B2
US 12,577,622 · App. 17/493,826 · Granted Mar 17, 2026

Detecting cancer risk

Inventors: Elisha Hughes (Salt Lake City, UT); Alexander Gutin (Salt Lake City, UT)
Assignee: Myriad Genetics, Inc.
C12Q1/6886C12Q1/6827C12Q1/6883C12Q2600/156C12Q2600/158
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,577,622
App. No.
17/493,826
Granted
Mar 17, 2026
Kind
B2
Abstract

The present disclosure relates to methods, kits, and systems for assessing the risk of a human subject for developing a cancer, including genetic risk assessment, clinical risk assessment, and combinations of both to improve risk analysis.

Claims (20)

1 . A method comprising:

genotyping a biological sample comprising DNA for test loci in a panel of single nucleotide polymorphisms (SNPs), wherein the biological sample is from a subject who has a familial history of breast cancer, wherein the subject has previously been determined to not harbor a pathogenic mutation in BRCA1 or BRCA2, wherein the panel of SNPs consist of at least 40 and up to 400 SNPs, wherein the SNPs comprise: 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, and rs7707921, and wherein the method does not comprise genotyping more than 400 SNPs; and

sequencing DNA from the biological sample to detect the sequence for a plurality of test genes comprising at least two and up to all of APC, ATM, BAP1, BARD1, BMPRIA, 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.

2 . The method of claim 1 , wherein the subject has previously been determined to not harbor a pathogenic mutation in CHEK2, ATM or TP53.

3 . The method of claim 1 , wherein the subject has previously been determined to not harbor a pathogenic mutation in any of the following genes: BRCA1, BRCA2, CHEK2, ATM, NBN, PALB2, BARD1, BRIP1, PMS2, MSH2, MSH6, TP53, and MUYTH.

4 . The method of claim 1 , wherein genotyping comprises next generation sequencing.

5 . The method of claim 4 , wherein the next generation sequencing comprises sequencing genomic regions flanking each test locus.

6 . The method of claim 5 , wherein the genomic regions flanking each test locus comprise at least 200 nucleotides on one or both sides of each test locus.

7 . The method of claim 4 , wherein the next generation sequencing comprises pyrosequencing.

8 . The method of claim 1 , wherein genotyping comprises a method selected from Polymerase Chain Reaction (PCR), real-time PCR, allele-specific hybridization, strand displacement amplification (SDA), self-sustained sequence replication or single base extension.

9 . The method of claim 1 , wherein genotyping comprises a method selected from agarose electrophoresis, polyacrylamide gel electrophoresis, capillary electrophoresis or denaturing gradient gel electrophoresis.

10 . The method of claim 1 , wherein the panel of SNPs consists of 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, and rs6762644.

11 . A method comprising:

obtaining a DNA sample for genotyping each test locus in a panel of single nucleotide polymorphisms (SNPs) from a subject with a family history of breast cancer and prior determination of no pathogenic mutations in BRCA1 or BRCA2; and

detecting the genotype of the DNA for only the test locus in the panel of SNPs consisting of between at least 40 and up to 400 SNPs, wherein the SNPs comprise: 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, and rs11249433, wherein the method does not genotype the DNA for any additional SNPs beyond the up to 400 SNPs; and

sequencing DNA from the biological sample to detect the sequence for a plurality of test genes comprising at least two and up to all of 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.

12 . The method of claim 1 , wherein the panel further comprises one or more SNPs selected from 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, and rs6762644.

13 . The method of claim 1 , wherein the panel further comprises 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, and rs6762644.

14 . The method of claim 11 , wherein the panel further comprises one or more SNPs selected from 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, and rs6762644.

15 . The method of claim 11 , wherein the panel further comprises 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, and rs6762644.

Assignments (4)
SECURITY INTEREST Recorded Aug 1, 2025
From: MYRIAD GENETICS, INC.; MYRIAD GENETIC LABORATORIES, INC.; MYRIAD WOMEN’S HEALTH, INC.; ASSUREX HEALTH, INC.; GATEWAY GENOMICS, LLC
To: ORBIMED ROYALTY & CREDIT OPPORTUNITIES IV, LP, AS ADMINISTRATIVE AGENT FOR SECURED PARTIES
Reel/Frame 072309/0932 →
RELEASE OF SECURITY INTEREST IN PATENTS PREVIOUSLY RECORDED AT REEL/FRAME (064235/0032) Recorded Aug 1, 2025
From: JPMORGAN CHASE BANK, N.A., AS ADMINISTRATIVE AGENT
To: MYRIAD GENETICS, INC.; MYRIAD WOMEN’S HEALTH, INC.; GATEWAY GENOMICS, LLC; ASSUREX HEALTH, INC.
Reel/Frame 072331/0215 →
PATENT SECURITY AGREEMENT Recorded Jul 7, 2023
From: MYRIAD GENETICS, INC.; MYRIAD WOMEN'S HEALTH, INC.; GATEWAY GENOMICS, LLC; ASSUREX HEALTH, INC.
To: JPMORGAN CHASE BANK, N.A.
Reel/Frame 064235/0032 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 13, 2022
From: HUGHES, ELISHA; GUTIN, ALEXANDER
To: MYRIAD GENETICS, INC.
Reel/Frame 059589/0225 →
Continuity (5)
Division 15996193 · Jun 1, 2018
Provisional Application 62553249 · Sep 1, 2017
Provisional Application 62529272 · Jul 6, 2017
Provisional Application 62514577 · Jun 2, 2017
Related Publication 20220205043A1 · Jun 30, 2022
References Cited (77)
US 5310893A · Erlich et al. · 1994 [cited by applicant]
US 5451512A · Apple et al. · 1995 [cited by applicant]
US 5468613A · Erlich et al. · 1995 [cited by applicant]
US 5593839A · Hubbell et al. · 1997 [cited by applicant]
US 5604099A · Erlich et al. · 1997 [cited by applicant]
US 5733729A · Lipshutz et al. · 1998 [cited by applicant]
US 5744305A · Fodor et al. · 1998 [cited by applicant]
US 5795716A · Chee · 1998 [cited by applicant]
US 5974164A · Chee · 1999 [cited by applicant]
US 6066454A · Lipshutz et al. · 2000 [cited by applicant]
US 6090555A · Fiekowsky et al. · 2000 [cited by applicant]
US 6185561B1 · Balaban et al. · 2001 [cited by applicant]
US 6188783B1 · Balaban et al. · 2001 [cited by applicant]
US 6223127B1 · Berno · 2001 [cited by applicant]
US 6229911B1 · Balaban et al. · 2001 [cited by applicant]
US 6308170B1 · Balaban · 2001 [cited by applicant]
US 6420108B2 · Mack et al. · 2002 [cited by applicant]
US 10683549B2 · Allman · 2020 [cited by applicant]
US 20020183936A1 · Kulp et al. · 2002 [cited by applicant]
US 20030097222A1 · Craford et al. · 2003 [cited by applicant]
US 20030100995A1 · Loraine et al. · 2003 [cited by applicant]
US 20030120432A1 · Zhou et al. · 2003 [cited by applicant]
US 20040049354A1 · Loraine et al. · 2004 [cited by applicant]
US 20150307947A1 · Basu · 2015 [cited by examiner]
US 20160222469A1 · Allman · 2016 [cited by applicant]
EP 0235726B1 · 1987 [cited by applicant]
WO WO8911548A1 · 1989 [cited by applicant]
Michailidou et al Nature Genetics. 2015. 47(4): 373-380, Online Methods, and Supplemental material, 81 pages (Year: 2015). [cited by examiner]
Trujillano et al J Mol Diagnostics. Mar. 2015. 17(2): 162-170 (Year: 2015). [cited by examiner]
U.S. Appl. No. 15/996,157, filed Jun. 1, 2017, Huges; Elisha. [cited by applicant]
Campa, et al., “Genetic risk variants associated with in situ breast cancer”, Breast Cancer Research; 2015; 17:82: p. 1-10. (Year: 2015). [cited by applicant]
Gerhardus, et al., “Diagnostic accuracy of methods for the detection of BRCA1 and BRCA2 mutations: a systematic review”, European Journal of Human Genetics; 2007; 15, 619-627. (Year: 2007). [cited by applicant]
Kuchenbaecker, et al., “Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers”, Breast Cancer Research; 2014; 16; 3416: p. 1-27. (Year: 2014… [cited by applicant]
Langdahl, et al., “Osteoporotic Fractures Are Associated with an 86-Base Pair Repeat Polymorphism in the Interleukin-I-Receptor Antagonist Gene But Not with Polymorphisms in the Interleukin-1 f3 Gene”, Journal of Bone a… [cited by applicant]
Liang et al. GWAS in cancer: progress and challenges. Molecular Genetics and Genomics; 2020; 295: 537-561. (Year: 2020). [cited by applicant]
Michailidou, et al., “Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer”, Nat Genet.; 2015; 47(4): 373-380. (Year: 2015). [cited by applicant]
Wall, et al., Nature Reviews Genetics (2003) vol. 4, pp. 587-597. (Year: 2003). [cited by applicant]
U.S. Appl. No. 15/996,157, filed Jun. 1, 2018, Hughes et al. [cited by applicant]
Abravaya et al., “Detection of point mutations with a modified ligase chain reaction”, Nucleic Acids Research, vol. 23, No. 4, pp. 675-692. [cited by applicant]
Anonymous, “Breast cancer in families”, Breast Cancer Care, Jun. 2008, pp. 1-40. [cited by applicant]
Barany, “Genetic disease detection and DNA amplification using cloned thermostable ligase”, PNAS, vol. 88, pp. 189-193. [cited by applicant]
Chee et al., “Accessing Genetic Information with High-Density DNA Arrays”, Science, vol. 274, No. 5287, Oct. 25, 1996, pp. 610-614. [cited by applicant]
Chen et al., “Mapping translocation breakpoints by next-generation sequencing”, Genome Research, vol. 18, Mar. 7, 2008, pp. 1143-1149. [cited by applicant]
Drmanac et al., “Accurate sequencing by hybridization for DNA diagnostics and individual genomics”, Nature Biotechnology, vol. 16, Jan. 1998, pp. 54-58. [cited by applicant]
Drmanac et al., “DNA Sequencing Determination by Hybridization: A Strategy for Efficient Larqe-Scale Sequencinq.” Science, vol. 260, 1993, pp. 1649-1652. [cited by applicant]
Elliot et al., “Rapid Detection of the ACMG/ACOG-Recommended 23 CFTR Disease-Causing Mutations Using Ion Torrent Semiconductor Sequencing”, Journal of Biomolecular Techniques, vol. 23, Issue 1, Jan. 2012, pp. 24-30. [cited by applicant]
Flusberg et al., “Direct detection of DNA methylation during single-molecule, real-time sequencing”, Nature Methods, vol. 7, No. 6, Jun. 2010, pp. 461-465. [cited by applicant]
Fu et al., “Sequencing exons 5 to 8 of the p53 gene by MALDI-TOF mass spectrometry”, Nature Biotechnology, vol. 16, Apr. 1998, pp. 381-384. [cited by applicant]
Kaji et al., :Nanopillar, nanoball, and nanofibers for highly efficient analysis of biomolecules, Chemical Society Reviews, vol. 39, 2010, pp. 948-956. [cited by applicant]
Kim et al., “DHPLC Analysis of Adenomatous [cited by applicant]
Landegren et al., “A Ligase-Mediated Gene Detection Technique”, Science, vol. 241, No. 4869, Aug. 26, 1988, pp. 1077-1080. [cited by applicant]
Marras et al., “Multiplex detection of single-nucleotide variations using molecular beacons”, Genetic Analysis: Biomolecular Engineering, vol. 14, 1999, pp. 151-156. [cited by applicant]
Maskos et al., “A novel method for the parallel analysis of multiple mutations in multiple mutations in multiple samples”, Nucleic Acids Research, vol. 23, No. 9, Mar. 25, 1993, pp. 2269-2270. [cited by applicant]
Mavaddat et al., “Prediction of Breast Cancer Risk Based on Profiling With Common Genetic Variants”, JNCI J Natl Cancer Inst, vol. 107, No. 5, 2015, pp. 1-15. [cited by applicant]
Michalidou et al., “Large-scale genotyping identifies 41 new loci associated with breast cancer risk”, Nature Genetics, vol. 45, No. 4, Apr. 2013, pp. 353-363. [cited by applicant]
Moller et al., “The Heritability of Breast Cancer among Women in the Nordic Twin Study of Cancer”, Cancer Epidemiology, Biomarkers & Prevention, vol. 25, No. 1, Jan. 2016, pp. 145-150. [cited by applicant]
Myers et al., “Detection of Single Base Substitutions by Ribonuclease Cleavage at Mismatches in RNA: DNA Duplexes”, Science, vol. 230, No. 4731, Dec. 13, 1985, pp. 1242-1246. [cited by applicant]
Nikiforov et al., “Genetic Bit Analysis: a solid phase method for typing single nucleotide polymorphisms”, Nucleic Acids Research, vol. 22, No. 20, Sep. 7, 1994, pp. 4167-4175. [cited by applicant]
Orita et al., “Rapid and Sensitive Detection of Point Mutations and DNA Polymorphisms Using the Polymerase Chain Reaction”, Genomics, vol. 5, Aug. 1, 1989, pp. 874-879. [cited by applicant]
Piatek et al., “Molecular beacon sequence analysis for detecting drug resistance in [cited by applicant]
Porreca et al., “Polony DNA Sequencing” Current Protocols in Molecular Biology, Supplement 76, Chapter 7, Unit 7.8, 2006, 22 pages. [cited by applicant]
Saiki et al., “Analysis of enzymatically amplified B-globin and HLA-DQ a DNA with allele-specific oligonucleotide probes”, Nature, vol. 324, Nov. 13, 1986, pp. 163-166. [cited by applicant]
Saiki et al., “Genetic analysis of amplified DNA with immobilized sequence-specific oligonucleotide probes”, Proc. Natl. Acad. Sci., Aug. 1989, vol. 86, pp. 6230-6234. [cited by applicant]
Sambrook et al., “Molecular Cloning. A Laboratory Manual”, 2nd ed., Cold Spring Harbor Laboratory, New York, 1989. [cited by applicant]
Schneble et al., “Current Approaches and Challenges in Early Detection of Breast Cancer Recurrence”, Journal of Cancer, vol. 5, Mar. 16, 2014, pp. 281-290. [cited by applicant]
Shendure et al., “Next-generation DNA sequencing”, Nature Biotechnology, vol. 26, No. 10, Oct. 2008, pp. 1135-1145. [cited by applicant]
Srivatsan et al., “High-Precision, Whole-Genome Sequencing of Laboratory Strains Facilitates Genetic Studies”, PLoS Genetics, vol. 4, Issue 8, Aug. 2008, pp. 1-14. [cited by applicant]
Stoneking et al., “Population Variation of Human mtDNA Control Region Sequences Detected by Enzymatic Amplification and Sequence-specific Oligonucleotide Probes”, Am. J. Hum. Genet., 1991, vol. 48, pp. 370-382. [cited by applicant]
Tapp et al., “Homogeneous Scoring of Single-Nucleotide Polymorphisms: Comparison of the 5'-Nuclease TaqMan Assay and Molecular Beacon Probes”, BioTechniques, vol. 28, Apr. 2000, pp. 732-738. [cited by applicant]
Tyagi et al., “Molecular Beacons: Probes that Fluoresce upon Hybridization”, Nature Biotechnology, vol. 14, Mar. 1996, pp. 303-308. [cited by applicant]
Tyagi et al., “Multicolor molecular beacons for allele discrimination”, Nature Biotechnology, vol. 16, Jan. 1998, pp. 49-53. [cited by applicant]
Visvanathan et al., “American Society of Clinical Oncology Clinical Practice Guideline Update on the Use of Pharmacologic Interventions Including Tamoxifen, Raloxifene, and Aromatase Inhibition for Breast Cancer Risk Re… [cited by applicant]
Wallace et al., “Hybridization of synthetic oligodeoxyribonucleotides to 174 DNA: the effect of single base pair mismatch”, Nucleic Acids Research, vol. 6, No. 11, 1978, pp. 3543-3557. [cited by applicant]
Wanunu, Meni, “Nanopores: A journey towards DNA sequencing”, vol. 9, May 2012, pp. 125-158. [cited by applicant]
Xu et al., “A fast and accurate SNP detection algorithm for next-generation sequencing data”, Nature Communications 2012, vol. 3, No. 1258, pp. 1-9. [cited by applicant]
Zimmerman et al., “Methods in Molecular and Cellular Biology”, vol. 3, No. 1, 1992, pp. 39-42. [cited by applicant]
Judkins et al., “Development and analytical validation of a 25-gene next generation sequencing panel that includes the BRCA1 and BRCA2 genes to assess hereditary cancer risk,” BMC Cancer, 15:215, 11 pages (2015). [cited by applicant]