Germline Mutations in PALB2, BRCA1, and RAD51C, Which Regulate DNA Recombination Repair, in Patients With Gastric Cancer

Ruta Sahasrabudhe; Paul Lott; Mabel Bohorquez; Ted Toal; Ana P. Estrada; John J. Suarez; Alejandro Brea-Fernández; José Cameselle-Teijeiro; Carla Pinto; Irma Ramos; Alejandra Mantilla; Rodrigo Prieto; Alejandro Corvalan; Enrique Norero; Carolina Alvarez; Teresa Tapia; Pilar Carvallo; Luz M. Gonzalez; Alicia Cock-Rada; Angela Solano; Florencia Neffa; Adriana Della Valle; Chris Yau; Gabriela Soares; Alexander Borowsky; Nan Hu; Li Ji He; Xiao You Han; Magdalena Echeverry; Mabel Bohorquez; Rodrigo Prieto; John Suarez; Gilbert Mateus; Maria Mercedes Bravo; Fernando Bolaños; Alejandro Vélez; Alejandro Corvalan; Pilar Carvallo; Javier Torres; Luis G. Carvajal-Carmona; Philip R. Taylor; Alisa M. Goldstein; Clara Ruiz-Ponte; Manuel R. Teixeira

doi:10.1053/j.gastro.2016.12.010

Germline Mutations in PALB2, BRCA1, and RAD51C, Which Regulate DNA Recombination Repair, in Patients With Gastric Cancer

Ruta Sahasrabudhe, Paul Lott, Mabel Bohorquez, Ted Toal, Ana P. Estrada, John J. Suarez, Alejandro Brea-Fernández, José Cameselle-Teijeiro, Carla Pinto, Irma Ramos, Alejandra Mantilla, Rodrigo Prieto, Alejandro Corvalan, Enrique Norero, Carolina Alvarez, Teresa Tapia, Pilar Carvallo, Luz M. Gonzalez, Alicia Cock-Rada, Angela SolanoFlorencia Neffa, Adriana Della Valle, Chris Yau, Gabriela Soares, Alexander Borowsky, Nan Hu, Li Ji He, Xiao You Han, Magdalena Echeverry, Mabel Bohorquez, Rodrigo Prieto, John Suarez, Gilbert Mateus, Maria Mercedes Bravo, Fernando Bolaños, Alejandro Vélez, Alejandro Corvalan, Pilar Carvallo, Javier Torres, Luis G. Carvajal-Carmona, Philip R. Taylor, Alisa M. Goldstein, Clara Ruiz-Ponte, Manuel R. Teixeira

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Resumen

Up to 10% of cases of gastric cancer are familial, but so far, only mutations in CDH1 have been associated with gastric cancer risk. To identify genetic variants that affect risk for gastric cancer, we collected blood samples from 28 patients with hereditary diffuse gastric cancer (HDGC) not associated with mutations in CDH1 and performed whole-exome sequence analysis. We then analyzed sequences of candidate genes in 333 independent HDGC and non-HDGC cases. We identified 11 cases with mutations in PALB2, BRCA1, or RAD51C genes, which regulate homologous DNA recombination. We found these mutations in 2 of 31 patients with HDGC (6.5%) and 9 of 331 patients with sporadic gastric cancer (2.8%). Most of these mutations had been previously associated with other types of tumors and partially co-segregated with gastric cancer in our study. Tumors that developed in patients with these mutations had a mutation signature associated with somatic homologous recombination deficiency. Our findings indicate that defects in homologous recombination increase risk for gastric cancer.

Idioma original	Inglés
Páginas (desde-hasta)	983-986.e6
Publicación	Gastroenterology
Volumen	152
N.º	5
DOI	https://doi.org/10.1053/j.gastro.2016.12.010
Estado	Publicada - 1 abr. 2017

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© 2017 AGA Institute

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Sahasrabudhe, R., Lott, P., Bohorquez, M., Toal, T., Estrada, A. P., Suarez, J. J., Brea-Fernández, A., Cameselle-Teijeiro, J., Pinto, C., Ramos, I., Mantilla, A., Prieto, R., Corvalan, A., Norero, E., Alvarez, C., Tapia, T., Carvallo, P., Gonzalez, L. M., Cock-Rada, A., ... Teixeira, M. R. (2017). Germline Mutations in PALB2, BRCA1, and RAD51C, Which Regulate DNA Recombination Repair, in Patients With Gastric Cancer. Gastroenterology, 152(5), 983-986.e6. https://doi.org/10.1053/j.gastro.2016.12.010

@article{f08174525a6341d1b0d62edcfcf08d00,

title = "Germline Mutations in PALB2, BRCA1, and RAD51C, Which Regulate DNA Recombination Repair, in Patients With Gastric Cancer",

abstract = "Up to 10% of cases of gastric cancer are familial, but so far, only mutations in CDH1 have been associated with gastric cancer risk. To identify genetic variants that affect risk for gastric cancer, we collected blood samples from 28 patients with hereditary diffuse gastric cancer (HDGC) not associated with mutations in CDH1 and performed whole-exome sequence analysis. We then analyzed sequences of candidate genes in 333 independent HDGC and non-HDGC cases. We identified 11 cases with mutations in PALB2, BRCA1, or RAD51C genes, which regulate homologous DNA recombination. We found these mutations in 2 of 31 patients with HDGC (6.5%) and 9 of 331 patients with sporadic gastric cancer (2.8%). Most of these mutations had been previously associated with other types of tumors and partially co-segregated with gastric cancer in our study. Tumors that developed in patients with these mutations had a mutation signature associated with somatic homologous recombination deficiency. Our findings indicate that defects in homologous recombination increase risk for gastric cancer.",

keywords = "Interaction, Stomach, Tumor, WES",

author = "Ruta Sahasrabudhe and Paul Lott and Mabel Bohorquez and Ted Toal and Estrada, {Ana P.} and Suarez, {John J.} and Alejandro Brea-Fern{\'a}ndez and Jos{\'e} Cameselle-Teijeiro and Carla Pinto and Irma Ramos and Alejandra Mantilla and Rodrigo Prieto and Alejandro Corvalan and Enrique Norero and Carolina Alvarez and Teresa Tapia and Pilar Carvallo and Gonzalez, {Luz M.} and Alicia Cock-Rada and Angela Solano and Florencia Neffa and {Della Valle}, Adriana and Chris Yau and Gabriela Soares and Alexander Borowsky and Nan Hu and He, {Li Ji} and Han, {Xiao You} and Magdalena Echeverry and Mabel Bohorquez and Rodrigo Prieto and John Suarez and Gilbert Mateus and Bravo, {Maria Mercedes} and Fernando Bola{\~n}os and Alejandro V{\'e}lez and Alejandro Corvalan and Pilar Carvallo and Javier Torres and Carvajal-Carmona, {Luis G.} and Taylor, {Philip R.} and Goldstein, {Alisa M.} and Clara Ruiz-Ponte and Teixeira, {Manuel R.}",

note = "Publisher Copyright: {\textcopyright} 2017 AGA Institute",

year = "2017",

month = apr,

day = "1",

doi = "10.1053/j.gastro.2016.12.010",

language = "Ingl{\'e}s",

volume = "152",

pages = "983--986.e6",

journal = "Gastroenterology",

issn = "0016-5085",

publisher = "W.B. Saunders Ltd",

number = "5",

}

Sahasrabudhe, R, Lott, P, Bohorquez, M, Toal, T, Estrada, AP, Suarez, JJ, Brea-Fernández, A, Cameselle-Teijeiro, J, Pinto, C, Ramos, I, Mantilla, A, Prieto, R, Corvalan, A, Norero, E, Alvarez, C, Tapia, T, Carvallo, P, Gonzalez, LM, Cock-Rada, A, Solano, A, Neffa, F, Della Valle, A, Yau, C, Soares, G, Borowsky, A, Hu, N, He, LJ, Han, XY, Echeverry, M, Bohorquez, M, Prieto, R, Suarez, J, Mateus, G, Bravo, MM, Bolaños, F, Vélez, A, Corvalan, A, Carvallo, P, Torres, J, Carvajal-Carmona, LG, Taylor, PR, Goldstein, AM, Ruiz-Ponte, C & Teixeira, MR 2017, 'Germline Mutations in PALB2, BRCA1, and RAD51C, Which Regulate DNA Recombination Repair, in Patients With Gastric Cancer', Gastroenterology, vol. 152, n.º 5, pp. 983-986.e6. https://doi.org/10.1053/j.gastro.2016.12.010

TY - JOUR

T1 - Germline Mutations in PALB2, BRCA1, and RAD51C, Which Regulate DNA Recombination Repair, in Patients With Gastric Cancer

AU - Sahasrabudhe, Ruta

AU - Lott, Paul

AU - Bohorquez, Mabel

AU - Toal, Ted

AU - Estrada, Ana P.

AU - Suarez, John J.

AU - Brea-Fernández, Alejandro

AU - Cameselle-Teijeiro, José

AU - Pinto, Carla

AU - Ramos, Irma

AU - Mantilla, Alejandra

AU - Prieto, Rodrigo

AU - Corvalan, Alejandro

AU - Norero, Enrique

AU - Alvarez, Carolina

AU - Tapia, Teresa

AU - Carvallo, Pilar

AU - Gonzalez, Luz M.

AU - Cock-Rada, Alicia

AU - Solano, Angela

AU - Neffa, Florencia

AU - Della Valle, Adriana

AU - Yau, Chris

AU - Soares, Gabriela

AU - Borowsky, Alexander

AU - Hu, Nan

AU - He, Li Ji

AU - Han, Xiao You

AU - Echeverry, Magdalena

AU - Bohorquez, Mabel

AU - Prieto, Rodrigo

AU - Suarez, John

AU - Mateus, Gilbert

AU - Bravo, Maria Mercedes

AU - Bolaños, Fernando

AU - Vélez, Alejandro

AU - Corvalan, Alejandro

AU - Carvallo, Pilar

AU - Torres, Javier

AU - Carvajal-Carmona, Luis G.

AU - Taylor, Philip R.

AU - Goldstein, Alisa M.

AU - Ruiz-Ponte, Clara

AU - Teixeira, Manuel R.

PY - 2017/4/1

Y1 - 2017/4/1

N2 - Up to 10% of cases of gastric cancer are familial, but so far, only mutations in CDH1 have been associated with gastric cancer risk. To identify genetic variants that affect risk for gastric cancer, we collected blood samples from 28 patients with hereditary diffuse gastric cancer (HDGC) not associated with mutations in CDH1 and performed whole-exome sequence analysis. We then analyzed sequences of candidate genes in 333 independent HDGC and non-HDGC cases. We identified 11 cases with mutations in PALB2, BRCA1, or RAD51C genes, which regulate homologous DNA recombination. We found these mutations in 2 of 31 patients with HDGC (6.5%) and 9 of 331 patients with sporadic gastric cancer (2.8%). Most of these mutations had been previously associated with other types of tumors and partially co-segregated with gastric cancer in our study. Tumors that developed in patients with these mutations had a mutation signature associated with somatic homologous recombination deficiency. Our findings indicate that defects in homologous recombination increase risk for gastric cancer.

AB - Up to 10% of cases of gastric cancer are familial, but so far, only mutations in CDH1 have been associated with gastric cancer risk. To identify genetic variants that affect risk for gastric cancer, we collected blood samples from 28 patients with hereditary diffuse gastric cancer (HDGC) not associated with mutations in CDH1 and performed whole-exome sequence analysis. We then analyzed sequences of candidate genes in 333 independent HDGC and non-HDGC cases. We identified 11 cases with mutations in PALB2, BRCA1, or RAD51C genes, which regulate homologous DNA recombination. We found these mutations in 2 of 31 patients with HDGC (6.5%) and 9 of 331 patients with sporadic gastric cancer (2.8%). Most of these mutations had been previously associated with other types of tumors and partially co-segregated with gastric cancer in our study. Tumors that developed in patients with these mutations had a mutation signature associated with somatic homologous recombination deficiency. Our findings indicate that defects in homologous recombination increase risk for gastric cancer.

KW - Interaction

KW - Stomach

KW - Tumor

KW - WES

UR - http://www.scopus.com/inward/record.url?scp=85016201532&partnerID=8YFLogxK

U2 - 10.1053/j.gastro.2016.12.010

DO - 10.1053/j.gastro.2016.12.010

M3 - Artículo en revista científica indexada

C2 - 28024868

AN - SCOPUS:85016201532

SN - 0016-5085

VL - 152

SP - 983-986.e6

JO - Gastroenterology

JF - Gastroenterology

IS - 5

ER -

Germline Mutations in PALB2, BRCA1, and RAD51C, Which Regulate DNA Recombination Repair, in Patients With Gastric Cancer

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