Candidate predisposing germline copy number variants in early onset colorectal cancer patients
Clin. transl. oncol. (Print)
; 19(5): 625-632, mayo 2017. tab, graf
Artículo
en Inglés
| IBECS
| ID: ibc-162197
Biblioteca responsable:
ES1.1
Ubicación: BNCS
ABSTRACT
Purpose. A great proportion of the heritability of colorectal cancer (CRC) still remains unexplained, and rare variants, as well as copy number changes, have been proposed as potential candidates to explain the so-called missing heritability. We aimed to identify rare high-to-moderately penetrant copy number variants (CNVs) in patients suspected of having hereditary CRC due to an early onset. Methods/patients. We have selected for genome-wide copy number analysis, 27 MMR-proficient early onset CRC patients (<50 years) without identifiable germline mutations in Mendelian genes related to this phenotype. Rare CNVs were selected by removing all CNVs detected at MAF >1% in the in-house control CNV database (n = 629 healthy controls). Copy number assignment was checked by duplex real-time quantitative PCR or multiplex ligation probe amplification. Somatic mutation analysis in candidate genes included loss of heterozygosity studies, point mutation screening, and methylation status of the promoter. Results. We have identified two rare germline deletions involving the AK3 and SLIT2 genes in two patients. The search for a second somatic mutational event in the corresponding CRC tumors showed loss of heterozygosity in AK3, and promoter hypermethylation in SLIT2. Both genes have been previously related to colorectal carcinogenesis. Conclusions. These findings suggest that AK3 and SLIT2 may be potential candidates involved in genetic susceptibility to CRC (AU)
RESUMEN
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Colección:
Bases de datos nacionales
/
España
Base de datos:
IBECS
Asunto principal:
Neoplasias Colorrectales
/
Neoplasias Colorrectales Hereditarias sin Poliposis
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Mutación de Línea Germinal
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Predisposición Genética a la Enfermedad
/
Micronúcleo Germinal
Tipo de estudio:
Estudio de etiología
/
Estudio pronóstico
Límite:
Adulto
/
Femenino
/
Humanos
/
Masculino
Idioma:
Inglés
Revista:
Clin. transl. oncol. (Print)
Año:
2017
Tipo del documento:
Artículo
Institución/País de afiliación:
Catalan Institute of Oncology/Spain
/
Hospital Clinic/Spain
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Hospital Clínico Universitario/Spain
/
Hospital General de Alicante/Spain
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Hospital Sant Pau/Spain
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Hospital del Mar/Spain
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Hospital do Meixoeiro/Spain
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Universidad de Santiago de Compostela (USC)/Spain
/
University of Illinois at Chicago/USA