495P - Contribution of rare germline copy number variants and single nucleotide polymorphisms to familial colorectal cancer

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Hereditary Syndromes
Colon and Rectal Cancer
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Presenter Rolando Rios Villacis
Citation Annals of Oncology (2014) 25 (suppl_4): iv165-iv166. 10.1093/annonc/mdu332
Authors R.A. Rios Villacis1, E.M. Santos2, B.M. Rossi3, D.M. Carraro4, L.P. Kowalski5, S.R. Rogatto4
  • 1Cipe - Research Center, AC Camargo Cancer Center, 01508-010 - São Paulo/BR
  • 2Oncology Center, Sirio-Libanes Hospital, São Paulo/BR
  • 3Department Of Oncogenetics, Barretos Cancer Hospital, São Paulo/BR
  • 4Cipe - Research Center, AC Camargo Cancer Center, São Paulo/BR
  • 5Department Of Head And Neck, AC Camargo Cancer Center, São Paulo/BR



Lynch Syndrome (LS) is the most common hereditary disease associated with colorectal carcinomas (CRC). Approximately 50% of cases presented mutations in mismatch repair (MMR) genes. Therefore, the molecular etiology of half of patients is still largely unknown, suggesting that other genetic or epigenetic hereditary factors might be associated with the cancer predisposition.


Germline copy number variations (CNVs) were screened in 58 LS patients negative for pathogenic mutations in MMR genes, using a CGH 4x180K platform (Agilent Technologies). Genomic data were analyzed with Genomic Workbench software. A CNV data of 100 healthy Brazilian women analyzed with the same platform and parameters were used as a reference group (Krepischi et al., 2012; Breast Cancer Res 14:R24). The results were compared with the Database of Genomic Variants (DGV-hg18). The CNVs were classified as rare if detected in <1% of DGV. Additionally, 10 SNPs classified as high CRC risk (rs961253, rs3802842, rs4444235, rs4779584, rs4939827, rs6983267, rs9929218, rs10411210, rs10795668 and rs16892766) were genotyped in 50 cases, using the TaqMan® SNP Genotyping Assay 5' nuclease technology (Applied Biosystems).


A reduced number of CNVs in cases (263; 4.5 ± 3.6 CNVs/individual) were found in comparison with the Brazilian reference dataset (706; 7.1 ± 3.2 CNVs/individual) (Mann-Whitney Test, p < 0.001). However, we identified a significantly higher number of rare CNVs per genome in cases (86) compared with the reference group (80) (Mann-Whitney Test, p < 0.001). Three rare CNVs, of the same size, were detected in at least two cases: 7p22.3, 9p21.3 and 14q13.1. Interestingly, 10 rare CNVs mapped on eight chromosomes and in different patients were entirely new. The SNP genotyping analysis revealed a median of 9.4 alleles of risk per case, ranging from 3 to 14. Six risk alleles were found in more than 50% of the cases.


These results suggested that patients with a proficient MMR profile, rare CNVs and SNPs might contribute to the risk of CRC development in Lynch syndrome patients.


All authors have declared no conflicts of interest.