Methods and materials for assessing and treating cancer

Abstract

Provided herein are methods and materials for detecting and/or treating subject (e.g., a human) having cancer. In some embodiments, methods and materials for identifying a subject as having cancer (e.g., a localized cancer) are provided in which the presence of member(s) of two or more classes of biomarkers are detected. In some embodiments, methods and materials for identifying a subject as having cancer (e.g., a localized cancer) are provided in which the presence of member(s) of at least one class of biomarkers and the presence of aneuploidy are detected. In some embodiments, methods described herein provide increased sensitivity and/or specificity in the detection of cancer in a subject (e.g. a human).

What is claimed is: 
     
         1 . A method of evaluating a subject for the presence of any of a plurality of cancers in a subject, comprising:
 detecting in a biological sample obtained from the subject the presence of one or more driver gene mutations in one or more driver genes, wherein each driver gene is associated with the presence of a cancer in the plurality of cancers;   thereby evaluating the subject for the presence of any of the plurality of cancers,   wherein the number of driver gene mutations detected is sufficient such that the sensitivity of detection of the cancer in the plurality of cancers with which each driver gene is associated is not substantially increased by the detection of one or more additional driver gene mutations.   
     
     
         2 . The method of  claim 1 , wherein detecting the one or more driver gene mutations comprises sequencing one or more regions of interest or amplicons comprising the driver gene mutation. 
     
     
         3 . The method of  claim 2 , wherein the number of regions of interest or amplicons sequenced is sufficient such that the sensitivity of detection of the cancer in the plurality of cancers with which each driver gene is associated with is not substantially increased by sequencing one or more additional regions of interest or amplicons. 
     
     
         4 . The method of  claim 1 , wherein the plurality of cancers comprises 4, 5, 6, 7 or 8 cancers. 
     
     
         5 . The method of  claim 1 , wherein the plurality of cancers is chosen from two or more of liver cancer, ovarian cancer, esophageal cancer, stomach cancer, pancreatic cancer, colorectal cancer, lung cancer, breast cancer, or prostate cancer. 
     
     
         6 . The method of  claim 3 , wherein at least 30 and not more than 400 regions of interest or amplicons from the driver genes are sequenced. 
     
     
         7 . The method of  claim 3 , wherein each region of interest or amplicon comprises 6-800 bp. 
     
     
         8 . The method of  claim 3 , wherein the number of regions of interest or amplicons sequenced is at least 500 bp and no more than 3000 bp. 
     
     
         9 . The method of  claim 1 , wherein at least 6 bp and no more than 300 bp in each driver gene is sequenced. 
     
     
         10 . The method of  claim 1 , wherein:
 (i) the subject has not yet been determined to have a cancer,   (ii) the subject has not yet been determined to harbor a cancer cell, or   (iii) the subject does not exhibit, or has not exhibited, a symptom associated with a cancer.   
     
     
         11 . The method of  claim 1 , wherein the one or more driver genes are chosen from a gene disclosed in Table 60 or 61. 
     
     
         12 . The method of  claim 1 , wherein the one or more driver genes comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 genes chosen from Tables 60 and 61. 
     
     
         13 . The method of  claim 12 , wherein the one or more driver genes comprise one or more of KRAS, PIK3CA, HRAS, CDKN2A, TP53, AKT1, CTNNB1, APC, EGFR, GNAS, PPP2R1A, BRAF, FBXM7, PTEN, or FGFR2. 
     
     
         14 . The method of  claim 1 , wherein the cancer of any of the plurality of cancers is chosen from: liver cancer, ovarian cancer, esophageal cancer, stomach cancer, pancreatic cancer, colorectal cancer, lung cancer, breast cancer, or prostate cancer. 
     
     
         15 . The method of  claim 1 , further comprising:
 a) detecting the level of each of one or more protein biomarkers in the biological sample, wherein the level of each protein biomarker is associated with the presence of a cancer of the plurality of cancers; and   b) identifying the presence of a cancer of the plurality of cancers in the subject when the presence of one or more protein biomarkers is detected.   
     
     
         16 . The method of  claim 15 , further comprising comparing the detected levels of each protein biomarker to a reference level for the protein biomarker. 
     
     
         17 . The method of  claim 1 , wherein the biological sample comprises one or more of:
 (i) a tumor sample, a circulating tumor DNA sample, a solid tumor biopsy sample, or a fixed tumor sample,   (ii) a blood sample,   (iii) an apheresis sample,   (iv) a cell-free DNA sample, or   (v) a protein sample.   
     
     
         18 . The method of  claim 15 , wherein the protein biomarker comprises one or more of: CA19-9, CEA, HGF, OPN, CA125, prolactin, TIMP-1, or MPO. 
     
     
         19 . The method of  claim 1 , wherein detecting the presence of one or more driver gene mutation comprises:
 a. assigning a unique identifier (UID) to each of a plurality of template molecules present in the sample;   b. amplifying each uniquely tagged template molecule to create UID-families; and   c. redundantly sequencing the amplification products.   
     
     
         20 . A method of evaluating a subject for the presence of any of a plurality of cancers in a subject, comprising:
 (a) detecting in a biological sample obtained from the subject the presence of one or more driver gene mutations in one or more driver genes, wherein the one or more driver genes comprise one or more of KRAS, PIK3CA, HRAS, CDKN2A, TP53, AKT1, CTNNB1, APC, EGFR, GNAS, PPP2R1A, BRAF, FBXM7, PTEN, or FGFR2, and wherein each driver gene is associated with the presence of a cancer in the plurality of cancers; and   (b) detecting the level of one or more protein biomarkers in a biological sample, wherein the one or more protein biomarkers comprise one or more of CA19-9, CEA, HGF, OPN, CA125, prolactin, TIMP-1, or MPO, and wherein the level of each protein biomarker is associated with the presence of a cancer of the plurality of cancers,   thereby evaluating the subject for the presence of any of the plurality of cancers,   wherein the presence of a cancer of the plurality of cancers is identified when the presence of one or more driver gene mutations and the level of one or more of the protein biomarkers is detected.