GRCh38 · COSMIC v94

Summary

This section shows a summary for the selected study (COSU identifier) or publication (COSP identifier). Studies may have been performed by the Sanger Institute Cancer Genome Project, or imported from the ICGC/TCGA. You can see more information on the help pages.

Reference
Distinct patterns of somatic alterations in a lymphoblastoid and a tumor genome derived from the same individual.
Paper ID
COSP25950
Authors
Galante PA, Parmigiani RB, Zhao Q, Caballero OL, de Souza JE, Navarro FC, Gerber AL, Nicolás MF, Salim AC, Silva AP, Edsall L, Devalle S, Almeida LG, Ye Z, Kuan S, Pinheiro DG, Tojal I, Pedigoni RG, de Sousa RG, Oliveira TY, de Paula MG, Ohno-Machado L, Kirkness EF, Levy S, da Silva WA, Vasconcelos AT, Ren B, Zago MA, Strausberg RL, Simpson AJ, de Souza SJ and Camargo AA
Affiliation
Ludwig Institute for Cancer Research, São Paulo Branch at Hospital Alemão Oswaldo Cruz, São Paulo 01323-903, Brazil.
Journal
Nucleic acids research, 2011;39(14):6056-68
ISSN: 1362-4962
PMID: 21493686 (view at PubMed or Europe PMC)
Abstract
Although patterns of somatic alterations have been reported for tumor genomes, little is known on how they compare with alterations present in non-tumor genomes. A comparison of the two would be crucial to better characterize the genetic alterations driving tumorigenesis. We sequenced the genomes of a lymphoblastoid (HCC1954BL) and a breast tumor (HCC1954) cell line derived from the same patient and compared the somatic alterations present in both. The lymphoblastoid genome presents a comparable number and similar spectrum of nucleotide substitutions to that found in the tumor genome. However, a significant difference in the ratio of non-synonymous to synonymous substitutions was observed between both genomes (P = 0.031). Protein-protein interaction analysis revealed that mutations in the tumor genome preferentially affect hub-genes (P = 0.0017) and are co-selected to present synergistic functions (P < 0.0001). KEGG analysis showed that in the tumor genome most mutated genes were organized into signaling pathways related to tumorigenesis. No such organization or synergy was observed in the lymphoblastoid genome. Our results indicate that endogenous mutagens and replication errors can generate the overall number of mutations required to drive tumorigenesis and that it is the combination rather than the frequency of mutations that is crucial to complete tumorigenic transformation.
Paper Status
Curated