The Cancer Genome Atlas
Publications

The Cancer Genome Atlas

Section Title: Publications
Table Section Text: None

Cancer Type Studied	Final Number Analyzed in Original Marker Paper	Data Publicly Available	TCGA Analysis Findings

Glioblastoma Multiforme	206	X	GBM subtypes Classical, Mesenchymal and Proneural are defined by EGFR, NF1, and PDGFRA/IDH1 mutations respectively; over 40% of tumors have mutations in chromatin-modifier genes; other frequently mutated genes include TP53, PlK3R1, PIK3CA, IDH1, PTEN, RB1, LZTR1

Lower Grade Glioma	293	X	Defined three subtypes correlating with patient outcomes: IDH1 mutant with 1p/19q deletion, IDH mutant without 1p/19q deletion, and IDH wildtype; IDH wildtype is genomically similar to glioblastoma

Breast Lobular Carcinoma	203	X	Lobular carcinoma distinct from ductal carcinoma; FOXA1 elevated in lobular carcinoma, GATA3 elevated in ductal carcinoma; lobular carcinoma enriched for PTEN loss and Akt activation

Breast Ductal Carcinoma	784	X	Four distinct genomic subtypes: basal, Her2, luminal A, luminal B; most common driver mutations TP53, PIK3CA, GATA3; basal subtype similar to serous ovarian cancer

Colorectal Adenocarcinoma	276	X	Colon and rectal cancers have similar genomic profiles; hypermutated subtype (16% of samples) mostly found in right colon and associated with favorable prognosis; new potential drivers: ARlD1A, SOX9, FAM123B/WTX; overexpression of: ERBB2, IGF2; mutations in the WNT pathway

Stomach Adenocarcinoma	295	X	Identified four subtypes: EBV characterized by Epstein-Barr virus infection, MSI (microsatellite instability) characterized by hypermutation, GS characterized by genomic stability, CIN characterized by chromosomal instability; CIN enriched for mutations in tyrosine kinases

Esophageal Carcinoma	164	X	Squamous cell and adenocarcinoma are molecularly distinct; squamous cell carcinomas were similar to head and neck squamous cell carcinomas and had frequent amplifications of CCND1, SOX2 and TP63; adenocarcinomas were similar to chromosomally unstable gastric adenocarcinoma and had frequent amplifications in ERBB2, VEGFA, GATA4, and GATA6

Ovarian Serous Cystadenocarcinoma	489	X	Mutations in TP53 occurred in 96% of the cases studied; mutations in BRCA1 and BRCA2 occurred in 21% of the cases and were associated with more favorable outcomes

Uterine Corpus Endometrial Carcinoma	373	X	Classified endometrial cancers into four categories: POLE ultramutated, MSI (microsatellite instability) hypermutated, copy-number low, and copy-number high; uterine serous carcinomas were similar to ovarian serous and basal-like Breast carcinomas and had less favorable prognoses than uterine endometrioid carcinomas

Cervical Squamous Cell Carcinoma and Adenocarcinoma	228	X	Identification of HPV-negative, endometrial-like cervical cancers with mutations in KRAS, ARID1A, and PTEN genes; amplification of CD274 and PDCD1LG2 immune checkpoint genes; alterations to genes including MED1, ERBB3, CASP8, HLA-A, and TGFBR2 and fusions involving lncRNA BCAR4; nearly three-quarters of samples had alterations in either one or both of the PI3K/MAPK and TGF-beta signaling pathways

Head and Neck Squamous Cell Carcinoma	279	X	Identified genomic features of HPV- and smoking-related cancers: HPV-positive characterized by shortened or deleted TRAF3, HPV-negative characterized by co-amplification of 11q13 and 11q22, smoking-related characterized by TP53 mutations, CDKN2A inactivation, and copy number alterations

Thyroid Carcinoma	496	X	Majority driven by RAS or BRAFV600E mutations; tumors driven by these mutations are distinct

Acute Myeloid Leukemia	200	X	Low mutation burden, with only 13 coding mutations on average per tumor; classified driver events into nine categories including transcription factor fusions, histone modifier mutations, spliceosome mutations and others

Cutaneous Melanoma	331	X	Established four subtypes: BRAF mutant, RAS mutant, NF1 mutant, and triple wild-type based on driver mutations; higher levels of immune lymphocyte infiltration correlated with better patient survival

Lung Adenocarcinoma	230	X	High mutation burden; 76% of tumors demonstrated activation of receptor tyrosine kinase pathways

Lung Squamous Cell Carcinoma	178	X	High average number of mutations and copy number aberrations; like ovarian serous cystadenocarcinoma, almost all lung squamous cell carcinomas contained a mutation in TP53; many tumors contained inactivating mutations in HLA-A that may help the cancer avoid immune detection

Clear Cell Renal Cell Carcinoma	446	X	Commonly mutated genes included VHL involved in oxygen sensing, SED2 involved in epigenetic modifications resulting in global hypomethylation, and genes of the PI3K/AKT/mTOR pathway; metabolic shift similar to the 'Warburg effect' correlates with a poor prognosis

Kidney Papillary Carcinoma	161	X	81% of type 1 tumors contained an alteration to MET; genomic profiles of type 2 tumors were heterogeneous, with alterations to CDKN2A, SETD2, TFE3, or increased expression of the NRF2–ARE pathway; loss of expression of CDKN2A and CpG island methylation phenotype were associated with poor outcome

Invasive Urothelial Bladder Cancer	131	X	Smoking is associated with increased risk; frequently mutated genes include TP53, which was inactivated in 76% of tumors and ERBB2 (HER2), genes in the receptor tyrosine kinase (RTK)/RAS pathways altered in 44% of tumors;

Prostate Adenocarcinoma	333	X	Highly heterogeneous with 26% of samples driven by unknown molecular alterations; 7 subtypes defined by ETS transcription factor gene fusions or mutations in SPOP, FOXA1, or IDH1; actionable lesions in the PI3K, MAPK, and DNA repair pathways

Chromophobe Renal Cell Carcinoma	66	X	Extremely low mutation burden; the carcinoma originates from more distal regions of the kidney compared to clear cell carcinoma, which is primarily from proximal regions; metabolic shift distinct from the 'Warburg effect' shift observed in clear cell carcinoma; TP53 and PTEN tumor suppressor genes were frequently mutated; TERT gene promoter was frequently altered

Adrenocortical Carcinoma	91	X	Overexpression of IGF2, mutations in TP53, PRKAR1A and other genes, and copy number alterations were common hallmarks; hypoploidy followed by whole genome doubling may be a driving mechanism of tumor development

Paraganglioma & Pheochromocytoma	173	X	Four distinct subtypes: Wnt-altered, cortical admixture, pseudohypoxia and kinase signaling; MAML3 fusion gene and CSDE1 somatic mutation define and drive the poor prognosis, Wnt-altered subtype

Cholangiocarcinoma	38	X	Low expression of CDKN2, BAP1, and ARID1 genes and overexpression of FGFR2 and IDH1/2 genes; four subtypes, one subtype characterized by alterations in IDH, silencing of ARID1A and low expression of other chromatin modifiers, and high mitochondrial gene expression; another subtype characterized by BAP1 mutations and FGFR2 gene fusions; the cancer may exist on a continuous spectrum with a subset of liver carcinomas with IDH or FGFR mutations

Liver Hepatocellular Carcinoma	363	X	TERT promoter mutations, identified in 44% of tumors, associated with increased elongation of telomeres and silencing of CDKN2A; TP53 commonly mutated or under-expressed; CTNNBB1 significantly mutated; many tumors with high levels of lymphocyte infiltration or overexpressed immune checkpoint genes CTLA4, PD-1, and PD-L1

Pancreatic Ductal Adenocarcinoma	150	X	Used deep and targeted sequencing to better analyze low neoplastic cellularity; KRAS mutations present in 93% of tumors; mutations in RREB1 or other members of RAS-MAPK signaling pathway

Uterine Carcinosarcoma	57	X	Identified a strong and varied degree of epithelial-mesenchymal transition; TP53 mutations present in 91% of samples; alterations in PI3K present in half of samples

Uveal Melanoma	80	X	Complex mutations in BAP1; identified distinct subdivisions of disomy 3 (D3) and monosomy 3 (M3) subtypes; in M3, mutually exclusive EIF1AX and SRSF2/SF3B1 mutations have distinct methylation profiles and prognoses

Thymoma	124	X

Sarcoma	206	X	TP53, ATRX, and RB1 among the few genes recurrently mutated across sarcoma types; copy number alterations frequently occurred in complex karyotype sarcomas, affecting p53 and RB1 cell cycle and other pathways; synovial sarcoma sarcomas expressed fusions in SSX1 or SSX2 and TERT; For dedifferentiated liposarcoma, JUN amplification associates with worse survival; altered PI3K-AKT-mTOR pathway in leiomyosarcoma; undifferentiated pleomorphic sarcoma and myxofibrosarcoma may be driven by alterations in the Hippo pathway

Mesothelioma	87	X

Testicular Germ Cell Cancer	150	X

Sentence(s)

TCGA analyzed 276 samples of colon and rectal cancers.

final_sentence: TCGA analyzed 276 samples of colon and rectal cancers.