Candidate predisposing germline copy number variants in early onset colorectal cancer patients
Por:
Brea-Fernandez, AJ, Fernandez-Rozadilla, C, Alvarez-Barona, M, Azuara, D, Ginesta, MM, Clofent, J, de Castro, L, Gonzalez, D, Andreu, M, Bessa, X, Llor, X, Xicola, R, Jover, R, Castells, A, Castellvi-Bel, S, Capella, G, Carracedo, A, Ruiz-Ponte, C
Publicada:
1 may 2017
Resumen:
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.
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.
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.
These findings suggest that AK3 and SLIT2 may be potential candidates involved in genetic susceptibility to CRC.
Filiaciones:
Brea-Fernandez, AJ:
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Grp Med Xenom USC, Santiago De Compostela, Spain
Fernandez-Rozadilla, C:
Hosp Clin Univ, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Fdn Publ Galega Med Xenom FPGMX SERGAS, Grp Med Xenom,IDIS, Edificio Consultas,Planta 2,Choupana S-N, Santiago De Compostela 15706, Spain
Alvarez-Barona, M:
Grp Med Xenom USC, Santiago De Compostela, Spain
Azuara, D:
IDIBELL, Catalan Inst Oncol, Translat Res Lab, Lhospitalet De Llobregat, Spain
Ginesta, MM:
IDIBELL, Catalan Inst Oncol, Translat Res Lab, Lhospitalet De Llobregat, Spain
Clofent, J:
Hosp Meixoeiro, Dept Gastroenterol, Vigo, Spain
Hosp Sagunto, Sect Digest Dis, Dept Internal Med, Valencia, Spain
de Castro, L:
Hosp Meixoeiro, Dept Gastroenterol, Vigo, Spain
Gonzalez, D:
Hosp Santa Creu & Sant Pau, Serv Patol Digest, Barcelona, Spain
Andreu, M:
Hosp del Mar, Dept Gastroenterol, Barcelona, Spain
Bessa, X:
Hosp del Mar, Dept Gastroenterol, Barcelona, Spain
Llor, X:
Univ Illinois, Sect Digest Dis & Nutr, Chicago, IL USA
Xicola, R:
Univ Illinois, Sect Digest Dis & Nutr, Chicago, IL USA
Jover, R:
Hosp Gen Alicante, Dept Gastroenterol, Alicante, Spain
Castells, A:
Univ Barcelona, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Ctr Invest Biomed Red Enfermedades & Hepat Digest, Dept Gastroenterol,Hosp Clin, Barcelona, Spain
Castellvi-Bel, S:
Univ Barcelona, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Ctr Invest Biomed Red Enfermedades & Hepat Digest, Dept Gastroenterol,Hosp Clin, Barcelona, Spain
Capella, G:
IDIBELL, Catalan Inst Oncol, Translat Res Lab, Lhospitalet De Llobregat, Spain
Carracedo, A:
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Grp Med Xenom USC, Santiago De Compostela, Spain
Hosp Clin Univ, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Fdn Publ Galega Med Xenom FPGMX SERGAS, Grp Med Xenom,IDIS, Edificio Consultas,Planta 2,Choupana S-N, Santiago De Compostela 15706, Spain
Grp Med Xenom USC, Santiago De Compostela, Spain
Ruiz-Ponte, C:
Hosp Clin Univ, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Fdn Publ Galega Med Xenom FPGMX SERGAS, Grp Med Xenom,IDIS, Edificio Consultas,Planta 2,Choupana S-N, Santiago De Compostela 15706, Spain
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