The landscape of cancer genes and mutational processes in breast cancer

By P. Stephens, P. Tarpey, H. Davies, P. van Loo, C. Greenman, David C. Wedge, S. Nik-Zainal, Sancha Martin, I. Varela, G. Bignell and 58 more. Nature, 2012

1,739 citations recorded by the source corpus.

All cancers carry somatic mutations in their genomes. A subset, known as driver mutations, confer clonal selective advantage on cancer cells and are causally implicated in oncogenesis, and the remainder are passenger mutations. The driver mutations and mutational processes operative in breast cancer have not yet been comprehensively explored. Here we examine the genomes of 100 tumours for somatic copy number changes and mutations in the coding exons of protein-coding genes. The number of somatic mutations varied markedly between individual tumours. We found strong correlations between mutation number, age at which cancer was diagnosed and cancer histological grade, and observed multiple mutational signatures, including one present in about ten per cent of tumours characterized by numerous mutations of cytosine at TpC dinucleotides. Driver mutations were identified in several new cancer genes including AKT2, ARID1B, CASP8, CDKN1B, MAP3K1, MAP3K13, NCOR1, SMARCD1 and TBX3. Among the 100 tumours, we found driver mutations in at least 40 cancer genes and 73 different combinations of mutated cancer genes. The results highlight the substantial genetic diversity underlying this common disease.

Subfields: Cancer Research, Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/289bc60d99b0136a11738200316ad57f692fde8d

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Citations in the corpus

Deciphering Signatures of Mutational Processes Operative in Human Cancer (2013, positive): “We therefore assessed the power of our approach to extract mutational processes from exome sequences using 100 recently sequenced breast cancer exomes (Stephens et al., 2012) containing (cid”
A community effort to assess and improve drug sensitivity prediction algorithms (2014, background): “However, identification of such biomarkers is complicated by substantial genomic and epigenomic heterogeneity in breast cancer 2,10,16,17 , indicating that multiple ‘drivers’ may serve as targets for breast cancer treatment.”
Evolution of the cancer stem cell model. (2014, background): “Similar approaches have been taken in breast cancer and other solid tumors to distinguish drivers from passengers (Nik-Zainal et al., 2012; Stephens et al., 2012).”
Mutational heterogeneity in cancer and the search for new cancer genes (2013, neutral): “…(GBM) 2 and lung adenocarcinoma 1,4 ; CSMD3 in ovarian cancer 2 ; PCLO in diffuse large B-cell lymphoma (DLBCL) 9 ; MUC16 in lung squamous carcinoma 11 , breast cancer 12 and DLBCL 8 ; MUC4 in melanoma 13 ; olfactory receptor OR2L13 in GBM 14 ; and TTN in breast cancer 12 and other tumor types 15 .”
Mutational Processes Molding the Genomes of 21 Breast Cancers (2012, background): “Cell 149, 979– 10% of ER-positive breast cancers (Stephens et al., 2012).”
Heterogeneity of genomic evolution and mutational profiles in multiple myeloma (2014, positive): “For a fraction of the variants ( B 25%), we used PCR followed by massively parallel pyrosequencing (Roche 454) 26 .”
Evolution and impact of subclonal mutations in chronic lymphocytic leukemia (2013, neutral): “Our study thus uncovers patterns of clonal evolution in CLL, providing insights into its stepwise transformation, and links the presence of subclones with adverse clinical outcomes.”
Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma (2013, positive): “In line with other tumor types 10,14,15 , pilocytic astrocytomas had genome-wide mutation rates that positively correlated with the age of the affected individual ( r = 0.42; P = 2.3 × 10 −5 , Pearson’s product-moment correlation; Supplementary Fig.”
Early dissemination seeds metastasis in breast cancer (2016, positive): “Phylogenetic trees were generated from copy number alterations (CNA), since Balb-NeuT tumours rarely display point mutations similar to human breast cancer 22 .”