Germline mutations in PALB2, BRCA1, and RAD51C, which regulate DNA recombination repair, in patients with gastric cancer
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 associa...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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AGA Institute
2016
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| _version_ | 1797070018090893312 |
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| author | Sahasrabudhe, R Lott, P Bohorquez, M Toal, T Estrada, A Suarez, 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 Cock-Rada, A Solano, A Neffa, F Della Valle, A Yau, C Soares, G Borowsky, A Hu, N He, L Han, X Latin American Gastric Cancer Genetics Collaborative Group Taylor, P Goldstein, A Torres, J Echeverry, M Ruiz-Ponte, C Teixeira, M Carvajal Carmona, L |
| author_facet | Sahasrabudhe, R Lott, P Bohorquez, M Toal, T Estrada, A Suarez, 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 Cock-Rada, A Solano, A Neffa, F Della Valle, A Yau, C Soares, G Borowsky, A Hu, N He, L Han, X Latin American Gastric Cancer Genetics Collaborative Group Taylor, P Goldstein, A Torres, J Echeverry, M Ruiz-Ponte, C Teixeira, M Carvajal Carmona, L |
| author_sort | Sahasrabudhe, R |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T22:33:01Z |
| format | Journal article |
| id | oxford-uuid:58e2f899-ede8-4c49-be0d-e95b574fb37a |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:33:01Z |
| publishDate | 2016 |
| publisher | AGA Institute |
| record_format | dspace |
| spelling | oxford-uuid:58e2f899-ede8-4c49-be0d-e95b574fb37a2022-03-26T17:06:33ZGermline mutations in PALB2, BRCA1, and RAD51C, which regulate DNA recombination repair, in patients with gastric cancerJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:58e2f899-ede8-4c49-be0d-e95b574fb37aEnglishSymplectic Elements at OxfordAGA Institute2016Sahasrabudhe, RLott, PBohorquez, MToal, TEstrada, ASuarez, JBrea-Fernández, ACameselle-Teijeiro, JPinto, CRamos, IMantilla, APrieto, RCorvalan, ANorero, EAlvarez, CTapia, TCarvallo, PGonzalez, LCock-Rada, ASolano, ANeffa, FDella Valle, AYau, CSoares, GBorowsky, AHu, NHe, LHan, XLatin American Gastric Cancer Genetics Collaborative GroupTaylor, PGoldstein, ATorres, JEcheverry, MRuiz-Ponte, CTeixeira, MCarvajal Carmona, LUp 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. |
| spellingShingle | Sahasrabudhe, R Lott, P Bohorquez, M Toal, T Estrada, A Suarez, 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 Cock-Rada, A Solano, A Neffa, F Della Valle, A Yau, C Soares, G Borowsky, A Hu, N He, L Han, X Latin American Gastric Cancer Genetics Collaborative Group Taylor, P Goldstein, A Torres, J Echeverry, M Ruiz-Ponte, C Teixeira, M Carvajal Carmona, L Germline mutations in PALB2, BRCA1, and RAD51C, which regulate DNA recombination repair, in patients with gastric cancer |
| title | Germline mutations in PALB2, BRCA1, and RAD51C, which regulate DNA recombination repair, in patients with gastric cancer |
| title_full | Germline mutations in PALB2, BRCA1, and RAD51C, which regulate DNA recombination repair, in patients with gastric cancer |
| title_fullStr | Germline mutations in PALB2, BRCA1, and RAD51C, which regulate DNA recombination repair, in patients with gastric cancer |
| title_full_unstemmed | Germline mutations in PALB2, BRCA1, and RAD51C, which regulate DNA recombination repair, in patients with gastric cancer |
| title_short | Germline mutations in PALB2, BRCA1, and RAD51C, which regulate DNA recombination repair, in patients with gastric cancer |
| title_sort | germline mutations in palb2 brca1 and rad51c which regulate dna recombination repair in patients with gastric cancer |
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