COSMIC v61 Release
COSMIC v61 focuses on whole genome screen publications with information from 17 major new reports, including the new TCGA Colon & Rectal cancer studies. In addition, the full literature on point mutations in PHF6 has been curated, along with 4 new gene fusion pairs.
Curated cancer genes
PHF6,encoding a plant homeodomain (PHD) factor containing 4 nuclear localization signals and 2 PHD-type finger domains, and with a proposed role in transcriptional regulation, has been identified as an X-linked tumour suppressor gene in T-cell acute lymphoblastic leukaemia and acute myeloid leukaemia. Mutations are evenly distributed throughout the gene with recurrent missense mutations in the second zinc finger domain. Mutation prevalence is greater in male than in female patients.
Newly curated gene fusionsFN1-ALK
A novel ALK fusion involving FN1 which encodes fibronectin, a ubiquitous component of extracellular matrix and plasma, has been found in ovarian malignant stromal sarcoma. The resultant fusion protein contains the amino-terminal 1201 amino acids of FN1 and the carboxyl-terminal 598 amino acids of ALK which include the transmembrane and cytoplasmic regions.KLC1-ALK
An additional ALK fusion partner has been identified in lung carcinoma. KLC1, encoding a member of the kinesin light chain family, fuses to the canonical ALK exon 20 recombination site in bronchioloalveolar carcinoma.FAM131B-BRAF
A recurrent oncogenic BRAF fusion involving FAM131B, a currently uncharacterized gene on chromosome 7q34, has been shown to be an alternative mechanism of MAPK pathway activation in pilocytic astrocytoma. In common with other BRAF and RAF1 fusions, the FAM131B-BRAF fusion product lacks the RAF auto-inhibitory domain. Of note is the small number of FAM131B exons, comprising mostly of 5' UTR, included in the fusion.UBE2L3-KRAS
An oncogenic KRAS fusion has been identified in a metastatic prostate cancer cell line. UBE2L3-KRAS encodes a protein encompassing most of the UBE2L3 protein, a member of the E2 ubiquitin-conjugating enzyme family, and full length KRAS.
Systematic screen curation
Focus on recent high-impact systematic screens:
Guichard et al (2012). Integrated analysis of somatic mutations and focal copy-number changes identifies key genes and pathways in hepatocellular carcinoma. Nat Genet. 44:694-8.
Jones et al (2012). Low-grade serous carcinomas of the ovary contain very few point mutations.J Pathol. 226:413-20.
Gui et al (2011). Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder. Nat Genet. 43:875-8.
Galante et al (2011). Distinct patterns of somatic alterations in a lymphoblastoid and a tumor genome derived from the same individual. Nucleic Acids Res. 39:6056-68.
Robinson et al (2012). Novel mutations target distinct subgroups of medulloblastoma. Nature. 488:43-8.
The Cancer Genome Atlas Network (2012). Comprehensive molecular characterization of human colon and rectal cancer.Nature. 487:330-7.
Pugh et al (2012). Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations.Nature. 488:106-10.
Zhang et al (2011). Key pathways are frequently mutated in high-risk childhood acute lymphoblastic leukemia: a report from the Children's Oncology Group.Blood. 118:3080-7.
Yip et al (2012). Concurrent CIC mutations, IDH mutations, and 1p/19q loss distinguish oligodendrogliomas from other cancers.J Pathol. 226:7-16.
Lee et al (2012). A remarkably simple genome underlies highly malignant pediatric rhabdoid cancers.J Clin Invest. 122:2983-8.
Bass et al (2011). Genomic sequencing of colorectal adenocarcinomas identifies a recurrent VTI1A-TCF7L2 fusion.Nat Genet. 43:964-8.
Zhang et al (2012). The genetic basis of early T-cell precursor acute lymphoblastic leukaemia.Nature. 481:157-63.
Jones et al (2012). Dissecting the genomic complexity underlying medulloblastoma.Nature. 488:100-5.
Fujimoto et al (2012). Whole-genome sequencing of liver cancers identifies etiological influences on mutation patterns and recurrent mutations in chromatin regulators.Nat Genet. 44:760-4.
Pe??a-Llopis et al (2012). BAP1 loss defines a new class of renal cell carcinoma. Nat Genet. 44:751-9.
Ong et al (2012). Exome sequencing of liver fluke-associated cholangiocarcinoma. Nat Genet. 44:690-3.
Duns et al (2012). Targeted exome sequencing in clear cell renal cell carcinoma tumors suggests aberrant chromatin regulation as a crucial step in ccRCC development.Hum Mutat. 33:1059-62.
The following genes have been updated in this release:
ABL1, ACVR1B, AKT1, ALK, APC, ARID1A, ASXL1, ATM, ATRX, AXIN1, BAP1, BRAF, BRCA1, BRCA2, CARD11, CBL, CDC73, CDH1, CDKN2A, CEBPA, CREBBP, CRLF2, CSF1R, CTNNA1,CTNNB1, CYLD, DAXX, DNMT3A, EGFR, EML4, EP300, ERBB2, ERG, EZH2, FAM123B, FBXW7, FGFR1, FGFR2, FGFR3, FLT3, GATA1, GATA2, GATA3, GNA11, GNAQ, GNAS, HNF1A, HRAS, IDH1, IDH2, IKZF1, IL7R, JAK1, JAK2, JAK3, KDR, KIT, KRAS, MAP2K4, MED12, MEN1, MET, MLH1, MLL2, MLL3, MPL, MSH2, MSH6, MYD88, NF1, NF2, NFE2L2, NOTCH1, NOTCH2, NPM1, NRAS, NTRK3, PAX5, PBRM1, PDGFRA, PHF6, PHOX2B, PIK3CA, PIK3R1, PPP2R1A, PRDM1, PRKAR1A, PTCH1, PTEN, PTPN11, RB1, RET, RUNX1, SETD2, SF3B1, SMAD4, SMARCA4, SMARCB1, SMO, SRC, SRSF2, STK11, SUFU, TET2, TNFAIP3, TP53, TSHR, U2AF1, VHL, WT1, ZRSR2
COSMIC v61 Total Statistics
|Genes ||22170 |
|Samples ||773098 |
|Mutations ||405271 |
|Unique Variants ||224649 |
|Papers ||14819 |
|Fusions ||8931 |
|Genomic Rearrangements ||7503 |
|Whole Genomes ||2556 |
Additional CGP resources:
The Cancer Gene Census, a listing of all genes known to be involved in cancer promotion
The Cancer Cell Line Project, defining key driver mutations in 800 common cancer cell lines
Cosmic Whole Genomes, all tumours with genome-wide somatic annotations
Genomics of Drug Sensitivity, Analysis of drug sensitivity data in human cancer cell lines.
CGP Copy Number Analysis in Cancer, examining tumours for gains or losses of genomic content