# US 12,110,554 B2 · Methods for classification of tissue samples as positive or negative for cancer > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,110,554 B2 - Document ID: US12110554B2 - Status: Granted - Kind: B2 - Application number: 17/157,876 - Filed: 2021-01-25 - Published: 2021-08-05 - Granted: 2024-10-08 - Earliest claimed: 2009-05-07 - Assignees: Veracyte, Inc. - Applicants: Veracyte, Inc. - Inventors: Giulia C. Kennedy; Bonnie H. Anderson; Darya I. Chudova; Eric T. Wang; Hui Wang; Moraima Pagan; Nusrat Rabbee; Jonathan I. Wilde - Web page: https://patentgrep.com/patent/US12110554B2 ## CPC - C12Q 1/6883: for diseases caused by alterations of genetic material - C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575) - C12Q 2600/112: Disease subtyping, staging or classification - C12Q 2600/156: Polymorphic or mutational markers - C12Q 2600/158: Expression markers - Y02A 90/10: Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation - C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES - Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE ## Abstract The present invention relates to compositions, kits, and methods for molecular profiling and cancer diagnostics, including but not limited to genomic DNA markers associated with cancer. In particular, the present invention provides molecular profiles associated with thyroid cancer, methods of determining molecular profiles, and methods of analyzing results to provide a diagnosis. ## Claims ### Claim 1 A method for processing or analyzing a tissue sample of a subject, comprising: (a) obtaining said tissue sample from said subject; (b) subjecting at least a portion of said tissue sample to a diagnostic screening process which indicates said tissue sample as ambiguous or indeterminate; (c) assaying one or more nucleic acid molecules derived from a nucleic acid sample from said tissue sample of said subject to generate a data set; (d) using a programmed computer to process said data set to identify (i) a level of expression of one or more gene expression products in said nucleic acid sample, and (ii) one or more genetic mutations in said nucleic acid sample; (e) using a trained algorithm, computer processing said level of expression and said one or more genetic mutations identified in (d) to generate a classification of said tissue sample as positive or negative for a cancer; and (f) electronically outputting a report that identifies said classification of said tissue sample as positive or negative for said cancer. ### Claim 2 (depends on 1) The method of claim 1, wherein said one or more genetic mutations comprise single nucleotide polymorphism (SNP), insertion deletion polymorphism (InDel), variable number of tandem repeat (VNTR), copy number variation (CNV), or any combination thereof. ### Claim 3 (depends on 1) The method of claim 1, wherein said one or more nucleic acid molecules comprise ribonucleic acid (RNA), deoxyribonucleic acid (DNA), or a combination or variant thereof. ### Claim 4 (depends on 3) The method of claim 3, wherein said RNA comprises microRNAs (miRNAs), ribosomal RNA (rRNA), transfer RNA (tRNA), messenger RNA (mRNA), or any combination thereof. ### Claim 5 (depends on 3) The method of claim 3, wherein said RNA has an RNA integrity number (RIN) of less than or equal to 6.0. ### Claim 6 (depends on 1) The method of claim 1, wherein (c) comprises sequencing said one or more nucleic acid molecules to generate said data set. ### Claim 7 (depends on 1) The method of claim 1, wherein said tissue sample comprises a thyroid tissue sample, a buccal tissue sample, or a combination thereof. ### Claim 8 (depends on 1) The method of claim 1, wherein said tissue sample comprises a fine needle aspirate (FNA) sample. ### Claim 9 (depends on 1) The method of claim 1, wherein said cancer is thyroid cancer or lung cancer. ### Claim 10 (depends on 1) The method of claim 1, wherein (c) comprises: (i) providing one or more binding agents that specifically bind to said one or more nucleic acid molecules, or a fragment or complement thereof, and (ii) contacting said one or more nucleic acid molecules with said one or more binding agents; and (iii) detecting one or more signals indicative of a presence or a quantity of said one or more nucleic acid molecules, or said fragment or complement. ### Claim 11 (depends on 10) The method of claim 10, wherein said one or more binding agents comprise oligonucleotides, aptamers, antibodies, peptide nucleic acids, pyranosyl RNA, or a combination or variant thereof. ### Claim 12 (depends on 1) The method of claim 1, wherein said one or more gene expression products or said one or more genetic mutations correspond to one or more genes of Tables 1, 3, 4, 5, or 6, or Lists 1-45, or a complement thereof. ### Claim 13 (depends on 1) The method of claim 1, wherein said tissue sample is classified as positive or negative for said cancer at an accuracy of at least 85%. ### Claim 14 (depends on 1) The method of claim 1, wherein said tissue sample is classified as positive or negative for said cancer at a negative predictive value (NPV) of at least 95%. ### Claim 15 (depends on 1) The method of claim 1, wherein said tissue sample is classified as positive or negative for said cancer at a specificity or sensitivity of at least 70%. ### Claim 16 (depends on 1) The method of claim 1, further comprising, administering a treatment plan or therapeutic intervention for said cancer to said subject, upon said tissue sample being classified as positive for said cancer. ### Claim 17 (depends on 16) The method of claim 16, wherein said treatment plan or therapeutic intervention comprises one or more of a surgery, a hormone or hormone agonist treatment, a chemotherapeutic treatment, and a radiation treatment. ### Claim 18 (depends on 1) The method of claim 1, further comprising monitoring said subject for development of said cancer upon said tissue sample being classified as negative for said cancer. ### Claim 19 (depends on 1) The method of claim 1, wherein said diagnostic screening process comprises a cytological analysis or an immunohistochemical method. ### Claim 20 (depends on 1) The method of claim 1, wherein said tissue sample is derived from a tumor, nodule, or lesion. ### Claim 21 (depends on 1) The method of claim 1, wherein (c) comprises (i) assaying RNA molecules derived from said nucleic acid sample to identify said level of expression of said one or more gene expression products, and (ii) assaying DNA molecules derived from said nucleic acid sample to identify said one or more genetic mutations.