Integrated Analysis of Germline and Tumor DNA Identifies New Candidate Genes Involved in Familial Colorectal Cancer.
colorectal cancer
computational genomics
germline–tumor analysis
mutational signatures
predisposition to disease
whole-exome sequencing
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
13 03 2019
13 03 2019
Historique:
received:
25
01
2019
revised:
08
03
2019
accepted:
09
03
2019
entrez:
16
3
2019
pubmed:
16
3
2019
medline:
16
3
2019
Statut:
epublish
Résumé
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).
Identifiants
pubmed: 30871259
pii: cancers11030362
doi: 10.3390/cancers11030362
pmc: PMC6468873
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Agència de Gestió d'Ajuts Universitaris i de Recerca
ID : 2018FI_B1_00213
Pays : International
Organisme : CIBEREHD
ID : CB06/04/0016
Pays : International
Organisme : Instituto de Salud Carlos III
ID : 17/00878
Pays : International
Organisme : Fundación Científica Asociación Española Contra el Cáncer
ID : GCB13131592CAST
Pays : International
Organisme : PERIS
ID : SLT002/16/00398
Pays : International
Organisme : Agència de Gestió d'Ajuts Universitaris i de Recerca
ID : GRPRE 2017SGR21
Pays : International
Organisme : Agència de Gestió d'Ajuts Universitaris i de Recerca
ID : GRC 2017SGR653
Pays : International
Organisme : European Cooperation in Science and Technology
ID : CA17118
Pays : International
Organisme : Generalitat de Catalunya
ID : CERCA programme
Pays : International
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