Research Papers:

Somatic mutations in early onset luminal breast cancer

Giselly Encinas, Veronica Y. Sabelnykova, Eduardo Carneiro de Lyra, Maria Lucia 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 Correa 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 and Maria Aparecida Azevedo Koike Folgueira _

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Oncotarget. 2018; 9:22460-22479. https://doi.org/10.18632/oncotarget.25123

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Giselly Encinas1,*, Veronica Y. Sabelnykova2,*, Eduardo Carneiro de Lyra3, Maria Lucia Hirata Katayama1, Simone Maistro1, Pedro Wilson Mompean de Vasconcellos Valle1, Gláucia Fernanda de Lima Pereira1, Lívia Munhoz Rodrigues1, Pedro Adolpho de Menezes Pacheco Serio1, Ana Carolina Ribeiro Chaves de Gouvêa1, Felipe Correa Geyer1, Ricardo Alves Basso3, Fátima Solange Pasini1, Maria del Pilar Esteves Diz1, Maria Mitzi Brentani1, João Carlos Guedes Sampaio Góes3, Roger Chammas1, Paul C. Boutros2,4,5 and Maria Aparecida Azevedo Koike Folgueira1

1Instituto do Cancer do Estado de Sao Paulo, Departamento de Radiologia e Oncologia, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil

2Ontario Institute for Cancer Research, Toronto, Canada

3Instituto Brasileiro de Controle do Câncer, São Paulo, Brazil

4Department of Medical Biophysics, University of Toronto, Toronto, Canada

5Department 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: [email protected]

Keywords: breast cancer; young patients; somatic mutation; germline mutation; luminal subtype

Received: September 26, 2017     Accepted: March 06, 2018     Published: April 27, 2018


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 BRCA1/2 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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