METHODS FOR ASSESSING GENOMIC INSTABILITIES IN TUMORS
The invention generally relates to methods for assessing genomic instabilities in a tumor sample. The invention may further be used to predict grade, stage, and prognosis of cancer in a patient. The invention further relates to cataloging the efficacy of therapeutics on specific genomic instabilities and generating a personalized therapeutic regimen for a cancer patient based upon their genomic instabilities.
1 . A method of assessing cancer in a patient, the method comprising:
analyzing a nucleic acid from a sample;
identifying one or more genomically unstable loci in the nucleic acid;
assigning a weighted value to each genomically unstable locus; and
assessing cancer based on the weighted values.
2 . The method according to claim 1 , wherein the weighed value is based on severity of the genomically unstable locus.
3 . The method according to claim 1 , wherein the weighted value is based on a type of genomic instability.
4 . The method according to claim 3 , wherein the type of genomic instability is selected from the group consisting of additions, deletions, substitutions, translocations, alterations, amplifications, and single nucleotide polymorphisms.
5 . The method according to claim 1 , wherein the weighted value is based on a location of the genomically unstable locus.
6 . The method according to claim 5 , wherein the location is selected from the group consisting of: location on a chromosome, proximity to telomeres, and proximity to known or suspected locations of genomic instabilities found in certain cancers.
7 . The method according to claim 1 , wherein the weighted value is based on a number of nucleotides within each genomically unstable locus.
8 . The method according to claim 1 , wherein analyzing comprises sequencing the nucleic acid.
9 . The method according to claim 8 , wherein sequencing is sequencing-by-synthesis.
10 . The method according to claim 8 , wherein identifying comprises comparing the sequenced nucleic acid to a reference nucleic acid to thereby identify the genomically unstable loci.
11 . The method according to claim 1 , wherein prior to the assigning step, the method further comprises categorizing the genomically unstable loci.
12 . The method according to claim 11 , further comprising deriving a weighted sum for each category.
13 . The method according to claim 11 , wherein categorizing is based on a type of genomic instability.
14 . The method according to claim 11 , wherein categorizing is based on a location of the genomically unstable locus.
15 . The method according to claim 1 , wherein the method is performed again at a later period in time, thereby monitoring progression or recurrence of the cancer.
16 . A method of assessing cancer in a patient, the method comprising:
analyzing a nucleic acid from a sample;
identifying one or more genomically unstable loci in the nucleic acid;
categorizing the genomically unstable loci;
assigning a weighted value to each category; and
assessing cancer based on the weighted values.
17 . The method according to claim 16 , wherein categorizing is based on a type of genomic instability.
18 . The method according to claim 16 , wherein categorizing is based on a location of the genomically unstable locus.
19 . The method according to claim 1 , wherein analyzing comprises sequencing the nucleic acid.
20 . The method according to claim 10 , wherein identifying comprises comparing the sequenced nucleic acid to a reference nucleic acid to thereby identify the genomically unstable loci.
21 . The method according to claim 1 , wherein the method is performed again at a later period of time, thereby monitoring progression or recurrence of the cancer.
22 . A method of assessing cancer in a patient, the method comprising:
analyzing a nucleic acid from a sample;
identifying one or more genomically unstable loci in the nucleic acid;
assigning a weighted value to each genomically unstable locus based on its location; and
assessing cancer based on the weighted values.
23 . The method according to claim 22 , wherein the location is selected from the group consisting of: location on a chromosome, proximity to telomeres, and proximity to known locations of genomic instabilities found in certain cancers
24 . The method according to claim 22 , wherein analyzing comprises sequencing the nucleic acid.
25 . The method according to claim 24 , wherein identifying comprises comparing the sequenced nucleic acid to a reference nucleic acid to thereby identify the genomically unstable loci.
26 . The method according to claim 22 , wherein the method is performed again at a later period of time, thereby monitoring progression or recurrence of the cancer.
27 . A method of assessing cancer in a patient, the method comprising:
analyzing a nucleic acid from a sample;
identifying one or more genomically unstable loci in the nucleic acid;
determining a total number of nucleotides within the genomically unstable loci; and
assessing cancer based on results of the determining step.
28 . The method according to claim 27 , wherein prior to the assessing step, the method further comprises subdividing the total number of nucleotides within the genomically unstable loci into categories.
29 . The method according to claim 28 , wherein the categories are selected from the group consisting of: coding v. non-coding and introns v. exons.
30 . The method according to claim 27 , wherein analyzing comprises sequencing the nucleic acid.
31 . The method according to claim 30 , wherein identifying comprises comparing the sequenced nucleic acid to a reference nucleic acid to thereby identify the genomically unstable loci.
32 . The method according to claim 27 , wherein the method is performed again at a later period of time, thereby monitoring progression or recurrence of the cancer.