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2019-03-13

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cc-by (c) Díaz Gay, Marcos et al., 2019
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/176253

Integrated Analysis of Germline and Tumor DNA Identifies New Candidate Genes Involved in Familial Colorectal Cancer

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Recurs relacionat

https://doi.org/10.3390/cancers11030362

Resum

Colorectal cancer (CRC) shows aggregation in some families but no alterations in the known hereditary CRC genes. We aimed to identify new candidate genes which are potentially involved in germline predisposition to familial CRC. An integrated analysis of germline and tumor whole-exome sequencing data was performed in 18 unrelated CRC families. Deleterious single nucleotide variants (SNV), short insertions and deletions (indels), copy number variants (CNVs) and loss of heterozygosity (LOH) were assessed as candidates for first germline or second somatic hits. Candidate tumor suppressor genes were selected when alterations were detected in both germline and somatic DNA, fulfilling Knudson's two-hit hypothesis. Somatic mutational profiling and signature analysis were also performed. A series of germline-somatic variant pairs were detected. In all cases, the first hit was presented as a rare SNV/indel, whereas the second hit was either a different SNV (3 genes) or LOH affecting the same gene (141 genes). BRCA2, BLM, ERCC2, RECQL, REV3L and RIF1 were among the most promising candidate genes for germline CRC predisposition. The identification of new candidate genes involved in familial CRC could be achieved by our integrated analysis. Further functional studies and replication in additional cohorts are required to confirm the selected candidates.

Matèries

Càncer colorectal, Nucleòtids, ADN

Matèries (anglès)

Colorectal cancer, Nucleotides, DNA

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Articles publicats en revistes (Fonaments Clínics)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))

Citació

DÍAZ GAY, Marcos, FRANCH EXPÓSITO, Sebastià, ARNAU COLLELL, Coral, PARK, Solip, SUPEK, Fran, MUÑOZ, Jenifer, BONJOCH GASSOL, Laia, GRATACÓS MULLERAS, Anna, SÁNCHEZ ROJAS, Paula a., ESTEBAN JURADO, Clara, OCAÑA, Teresa, CUATRECASAS FREIXAS, Miriam, VILA CASADESÚS, Maria, LOZANO SALVATELLA, Juan josé, PARRA, Genís, LAURIE, Steve, BELTRAN I AGULLÓ, Sergi, EPICOLON Consortium, CASTELLS GARANGOU, Antoni, BUJANDA, Luis, CUBIELLA, Joaquín, BALAGUER PRUNÉS, Francesc, CASTELLVÍ BEL, Sergi. Integrated Analysis of Germline and Tumor DNA Identifies New Candidate Genes Involved in Familial Colorectal Cancer. _Cancers_. 2019. Vol. 11, núm. 3, pàgs. 362. [consulta: 21 de gener de 2026]. ISSN: 2072-6694. [Disponible a: https://hdl.handle.net/2445/176253]

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