Somatic mutations in early onset luminal breast cancer

// 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.