Comprehensive Constitutional Genetic and Epigenetic Characterization of Lynch-Like Individuals.
Lynch syndrome
Lynch-like syndrome
cancer genes panel
epimutation
methylation
mismatch repair
next generation sequencing
variant of unknown significance
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
05 Jul 2020
05 Jul 2020
Historique:
received:
04
05
2020
revised:
27
06
2020
accepted:
02
07
2020
entrez:
9
7
2020
pubmed:
9
7
2020
medline:
9
7
2020
Statut:
epublish
Résumé
The causal mechanism for cancer predisposition in Lynch-like syndrome (LLS) remains unknown. Our aim was to elucidate the constitutional basis of mismatch repair (MMR) deficiency in LLS patients throughout a comprehensive (epi)genetic analysis. One hundred and fifteen LLS patients harboring MMR-deficient tumors and no germline MMR mutations were included. Mutational analysis of 26 colorectal cancer (CRC)-associated genes was performed. Pathogenicity of MMR variants was assessed by splicing and multifactorial likelihood analyses. Genome-wide methylome analysis was performed by the Infinium Human Methylation 450K Bead Chip. The multigene panel analysis revealed the presence of two MMR gene truncating mutations not previously found. Of a total of 15 additional MMR variants identified, five -present in 6 unrelated individuals- were reclassified as pathogenic. In addition, 13 predicted deleterious variants in other CRC-predisposing genes were found in 12 probands. Methylome analysis detected one constitutional
Identifiants
pubmed: 32635641
pii: cancers12071799
doi: 10.3390/cancers12071799
pmc: PMC7408773
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Ministerio de Economía y Competitividad
ID : SAF2012-33636, SAF2015-68016-R and SAF2016-80888-R
Organisme : RTICC Network
ID : RD12/0036/0031 and RD12/0036/0008
Organisme : the Spanish Association Against Cancer (AECC)
ID : 080253
Organisme : Government of Catalonia
ID : 2014SGR338, 2017SGR1282 and PERIS SLT002/16/0037
Organisme : Fundación Mutua Madrileña
ID : AP114252013
Organisme : Catalonian Health Department
ID : SLT002/16/00409
Organisme : FEDER funds -a way to build Europe- (cofunding)
ID : SAF2012-33636, SAF2015-68016-R and SAF2016-80888-R
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