Produção Nacional
Somatic mutations in early onset luminal breast cancer
2018; Impact Journals LLC; Volume: 9; Issue: 32 Linguagem: Inglês
10.18632/oncotarget.25123
ISSN1949-2553
AutoresGiselly Encinas, Veronica Y. Sabelnykova, Eduardo Carneiro de Lyra, Maria Lúcia Hirata Katayama, Simone Maistro, Pedro Wilson Mompean de Vasconcellos Valle, Gláucia Fernanda de Lima Pereira, Lívia Munhoz Rodrigues, Pedro Adolpho de Menezes Pacheco Serio, Ana Carolina Ribeiro Chaves de Gouvêa, Felipe C. Geyer, Ricardo Alves Basso, Fátima Solange Pasini, Maria del Pilar Esteves Diz, Maria Mitzi Brentani, João Carlos Guedes Sampaio Góes, Roger Chammas, Paul C. Boutros, Maria Aparecida Azevedo Koike Folgueira,
Tópico(s)DNA Repair Mechanisms
Resumo// Giselly Encinas 1, * , Veronica Y. Sabelnykova 2, * , Eduardo Carneiro de Lyra 3 , Maria Lucia Hirata Katayama 1 , Simone Maistro 1 , Pedro Wilson Mompean de Vasconcellos Valle 1 , Gláucia Fernanda de Lima Pereira 1 , Lívia Munhoz Rodrigues 1 , Pedro Adolpho de Menezes Pacheco Serio 1 , Ana Carolina Ribeiro Chaves de Gouvêa 1 , Felipe Correa Geyer 1 , Ricardo Alves Basso 3 , Fátima Solange Pasini 1 , Maria del Pilar Esteves Diz 1 , Maria Mitzi Brentani 1 , João Carlos Guedes Sampaio Góes 3 , Roger Chammas 1 , Paul C. Boutros 2, 4, 5 and Maria Aparecida Azevedo Koike Folgueira 1 1 Instituto do Cancer do Estado de Sao Paulo, Departamento de Radiologia e Oncologia, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil 2 Ontario Institute for Cancer Research, Toronto, Canada 3 Instituto Brasileiro de Controle do Câncer, São Paulo, Brazil 4 Department of Medical Biophysics, University of Toronto, Toronto, Canada 5 Department of Pharmacology and Toxicology, University of Toronto, Toronto, Canada * These authors have contributed equally to this work Correspondence to: Maria Aparecida Azevedo Koike Folgueira, email: maria.folgueira@fm.usp.br Keywords: breast cancer; young patients; somatic mutation; germline mutation; luminal subtype Received: September 26, 2017 Accepted: March 06, 2018 Published: April 27, 2018 ABSTRACT Breast cancer arising in very young patients may be biologically distinct; however, these tumors have been less well studied. We characterized a group of very young patients (≤ 35 years) for BRCA germline mutation and for somatic mutations in luminal ( HER2 negative) breast cancer. Thirteen of 79 unselected very young patients were BRCA 1/2 germline mutation carriers. Of the non- BRCA tumors, eight with luminal subtype ( HER2 negative) were submitted for whole exome sequencing and integrated with 29 luminal samples from the COSMIC database or previous literature for analysis. We identified C to T single nucleotide variants (SNVs) as the most common base-change. A median of six candidate driver genes was mutated by SNVs in each sample and the most frequently mutated genes were PIK3CA, GATA3, TP53 and MAP2K4 . Potential cancer drivers affected in the present non- BRCA tumors include GRHL2, PIK3AP1, CACNA1E , SEMA6D , SMURF2 , RSBN1 and MTHFD2. Sixteen out of 37 luminal tumors (43%) harbored SNVs in DNA repair genes, such as ATR, BAP1, ERCC6, FANCD2, FANCL, MLH1 , MUTYH, PALB2, POLD1, POLE , RAD9A, RAD51 and TP53 , and 54% presented pathogenic mutations (frameshift or nonsense) in at least one gene involved in gene transcription. The differential biology of luminal early-age onset breast cancer needs a deeper genomic investigation.
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