GRCh38 · COSMIC v98

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
Revealing the Molecular Portrait of Triple Negative Breast Tumors in an Understudied Population through Omics Analysis of Formalin-Fixed and Paraffin-Embedded Tissues.
Paper ID
COSP41330
Authors
Vaca-Paniagua F, Alvarez-Gomez RM, Maldonado-Martínez HA, Pérez-Plasencia C, Fragoso-Ontiveros V, Lasa-Gonsebatt F, Herrera LA, Cantú D, Bargallo-Rocha E, Mohar A, Durand G, Forey N, Voegele C, Vallée M, Le Calvez-Kelm F, McKay J, Ardin M, Villar S, Zavadil J and Olivier M
Affiliation
Group of Molecular Mechanisms and Biomarkers, International Agency for Research on Cancer, Lyon, France; Subdirección de Investigación Básica, Instituto Nacional de Cancerología, México D.F., México; Unidad de Biomedicina, FES-Iztacala, Universidad Nacional Autónoma de México (UNAM), México D.F., México.
Journal
PloS one, 2015;10(5):e0126762
ISSN: 1932-6203
PMID: 25961742 (view at PubMed or Europe PMC)
Abstract
Triple negative breast cancer (TNBC), defined by the lack of expression of the estrogen receptor, progesterone receptor and human epidermal receptor 2, is an aggressive form of breast cancer that is more prevalent in certain populations, in particular in low- and middle-income regions. The detailed molecular features of TNBC in these regions remain unexplored as samples are mostly accessible as formalin-fixed paraffin embedded (FFPE) archived tissues, a challenging material for advanced genomic and transcriptomic studies. Using dedicated reagents and analysis pipelines, we performed whole exome sequencing and miRNA and mRNA profiling of 12 FFPE tumor tissues collected from pathological archives in Mexico. Sequencing analyses of the tumor tissues and their blood pairs identified TP53 and RB1 genes as the most frequently mutated genes, with a somatic mutation load of 1.7 mutations/exome Mb on average. Transcriptional analyses revealed an overexpression of growth-promoting signals (EGFR, PDGFR, VEGF, PIK3CA, FOXM1), a repression of cell cycle control pathways (TP53, RB1), a deregulation of DNA-repair pathways, and alterations in epigenetic modifiers through miRNA:mRNA network de-regulation. The molecular programs identified were typical of those described in basal-like tumors in other populations. This work demonstrates the feasibility of using archived clinical samples for advanced integrated genomics analyses. It thus opens up opportunities for investigating molecular features of tumors from regions where only FFPE tissues are available, allowing retrospective studies on the search for treatment strategies or on the exploration of the geographic diversity of breast cancer.
Paper Status
Curated