dataset
posted on 2023-03-31, 01:07 authored by Cristian Suárez-Cabrera, Rita M. Quintana, Ana Bravo, M. Llanos Casanova, Angustias Page, Josefa P. Alameda, Jesús M. Paramio, Alicia Maroto, Javier Salamanca, Adam J. Dupuy, Angel Ramírez, Manuel Navarro Table in gff3 format showing all the transposon insertions in breast tumors as detected by gCIS analysis (S1); Clinical data for 32 human breast tumors (S2); Scoring of the immunohistochemical staining of human breast tumors with RASA1, TP53 and NF1 antibodies (S3); Association of RASA1 and NF1 expression with clinical-pathological characteristics of patients described in supplementary Table S2 (S4); Analysis of RASA1 putative copy number alterations in the breast invasive carcinoma dataset using cBioportal (S5); Analysis of RASA1 putative copy loss and TP53 mutations in the breast invasive carcinoma dataset using cBioportal (S6); Analysis of NF1 putative copy number alterations in the breast invasive carcinoma dataset using cBioportal (S7).
Funding
ERDF
Institute of Health Carlos III
Comunidad Autónoma de Madrid
Ministerio de Economía y Competitividad
History
ARTICLE ABSTRACT
RAS genes are mutated in 20% of human tumors, but these mutations are very rare in breast cancer. Here, we used a mouse model to generate tumors upon activation of a mutagenic T2Onc2 transposon via expression of a transposase driven by the keratin K5 promoter in a p53+/− background. These animals mainly developed mammary tumors, most of which had transposon insertions in one of two RASGAP genes, neurofibromin1 (Nf1) and RAS p21 protein activator (Rasa1). Immunohistochemical analysis of a collection of human breast tumors confirmed that low expression of RASA1 is frequent in basal (triple-negative) and estrogen receptor negative tumors. Bioinformatic analysis of human breast tumors in The Cancer Genome Atlas database showed that although RASA1 mutations are rare, allelic loss is frequent, particularly in basal tumors (80%) and in association with TP53 mutation. Inactivation of RASA1 in MCF10A cells resulted in the appearance of a malignant phenotype in the context of mutated p53. Our results suggest that alterations in the Ras pathway due to the loss of negative regulators of RAS may be a common event in basal breast cancer. Cancer Res; 77(6); 1357–68. ©2017 AACR.
