Abstract
This is an 11-year survey of molecular analysis of APC germline mutations for the province of Quebec done at the Molecular Pathology Unit of the Jewish General Hospital which offers genetic testing for hereditary forms of colorectal cancer for the whole of Quebec province. We report on 47 unique mutations seen in 66 families affected with familial adenomatous polyposis. Of these unique mutations, 60% are short indels, 28% are point mutations, and 6% are whole exon deletions. The absence of founder mutations and the variety of mutations encountered reinforce the value of RNA-based testing and the need for gene dosage techniques such as multiplex ligation-dependent probe amplification.
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References
Canadian Cancer Society’s Steering Committee (2010) Canadian Cancer Statistics 2010. Toronto
Lipton L, Tomlinson I (2006) The genetics of FAP and FAP-like syndromes. Fam Cancer 5(3):221–226
Beroud C, Soussi T (1996) APC gene: database of germline and somatic mutations in human tumors and cell lines. Nucleic Acids Res 24(1):121–124
Bertario L, Russo A, Sala P et al (2003) Multiple approach to the exploration of genotype-phenotype correlations in familial adenomatous polyposis. J Clin Oncol 21(9):1698–1707
Friedl W, Caspari R, Sengteller M et al (2001) Can APC mutation analysis contribute to therapeutic decisions in familial adenomatous polyposis? Experience from 680 FAP families. Gut 48(4):515–521
Nieuwenhuis MH, Vasen HF (2007) Correlations between mutation site in APC and phenotype of familial adenomatous polyposis (FAP): a review of the literature. Crit Rev Oncol Hematol 61(2):153–161
Aretz S, Stienen D, Uhlhaas S et al (2005) Large submicroscopic genomic APC deletions are a common cause of typical familial adenomatous polyposis. J Med Genet 42(2):185–192
Bunyan DJ, Eccles DM, Sillibourne J et al (2004) Dosage analysis of cancer predisposition genes by multiplex ligation-dependent probe amplification. Br J Cancer 91(6):1155–1159
Michils G, Tejpar S, Thoelen R et al (2005) Large deletions of the APC gene in 15% of mutation-negative patients with classical polyposis (FAP): a Belgian study. Hum Mutat 25(2):125–134
Pagenstecher C, Gadzicki D, Stienen D et al (2007) A complex rearrangement in the APC gene uncovered by multiplex ligation-dependent probe amplification. J Mol Diagn 9(1):122–126
Rozen S, Skaletsky H (2000) Primer3 on the WWW for general users and for biologist programmers. Methods Mol Biol 132:365–386
Laurent-Puig P, Beroud C, Soussi T (1998) APC gene: database of germline and somatic mutations in human tumors and cell lines. Nucleic Acids Res 26(1):269–270
Stenson PD, Ball EV, Howells K, Phillips AD, Mort M, Cooper DN (2009) The human gene mutation database: providing a comprehensive central mutation database for molecular diagnostics and personalized genomics. Hum Genom 4(2):69–72
Nugent KP, Phillips RK, Hodgson SV et al (1994) Phenotypic expression in familial adenomatous polyposis: partial prediction by mutation analysis. Gut 35(11):1622–1623
Lamlum H, Al Tassan N, Jaeger E et al (2000) Germline APC variants in patients with multiple colorectal adenomas, with evidence for the particular importance of E1317Q. Hum Mol Genet 9(15):2215–2221
Soravia C, Berk T, Madlensky L et al (1998) Genotype-phenotype correlations in attenuated adenomatous polyposis coli. Am J Hum Genet 62(6):1290–1301
Friedl W, Meuschel S, Caspari R et al (1996) Attenuated familial adenomatous polyposis due to a mutation in the 3’ part of the APC gene. A clue for understanding the function of the APC protein. Hum Genet 97(5):579–584
van der Luijt RB, Meera Khan P, Vasen HF et al (1996) Germline mutations in the 3’ part of APC exon 15 do not result in truncated proteins and are associated with attenuated adenomatous polyposis coli. Hum Genet 98(6):727–734
Brensinger JD, Laken SJ, Luce MC et al (1998) Variable phenotype of familial adenomatous polyposis in pedigrees with 3’ mutation in the APC gene. Gut 43(4):548–552
Spirio L, Olschwang S, Groden J et al (1993) Alleles of the APC gene: an attenuated form of familial polyposis. Cell 75(5):951–957
Kim DW, Kim IJ, Kang HC et al (2005) Mutation spectrum of the APC gene in 83 Korean FAP families. Hum Mutat 26(3):281
De Rosa M, Scarano MI, Panariello L et al (2003) The mutation spectrum of the APC gene in FAP patients from southern Italy: detection of known and four novel mutations. Hum Mutat 21(6):655–656
Gomez-Fernandez N, Castellvi-Bel S, Fernandez-Rozadilla C et al (2009) Molecular analysis of the APC and MUTYH genes in Galician and Catalonian FAP families: a different spectrum of mutations? BMC Med Genet 10:57
De Rosa M, Dourisboure RJ, Morelli G et al (2004) First genotype characterization of Argentinean FAP patients: identification of 14 novel APC mutations. Hum Mutat 23(5):523–524
Andresen PA, Heimdal K, Aaberg K et al (2009) APC mutation spectrum of Norwegian familial adenomatous polyposis families: high ratio of novel mutations. J Cancer Res Clin Oncol 135(10):1463–1470
Kanter-Smoler G, Fritzell K, Rohlin A et al (2008) Clinical characterization and the mutation spectrum in Swedish adenomatous polyposis families. BMC Med 6:10
Chong G, Jarry J, Marcus V et al (2009) High frequency of exon deletions and putative founder effects in French Canadian Lynch syndrome families. Hum Mutat 30(8):E797–E812
Beroud C, Hamroun D, Collod-Beroud G, Boileau C, Soussi T, Claustres M (2005) UMD (Universal Mutation Database): 2005 update. Hum Mutat 26(3):184–191
Schouten JP, McElgunn CJ, Waaijer R, Zwijnenburg D, Diepvens F, Pals G (2002) Relative quantification of 40 nucleic acid sequences by multiplex ligation-dependent probe amplification. Nucleic Acids Res 30(12):e57
Pineda M, Gonzalez S, Lazaro C, Blanco I, Capella G (2010) Detection of genetic alterations in hereditary colorectal cancer screening. Mutat Res 693(1–2):19–31
Acknowledgments
We would like to thank the April Family Funds for Colorectal Cancer. Additional thanks to Magali Breguet, Natasha Caminsky, Stephen DiNunzio with help in gathering data.
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The authors declare that they have no competing interests.
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Jarry, J., Brunet, JS., Laframboise, R. et al. A survey of APC mutations in Quebec. Familial Cancer 10, 659–665 (2011). https://doi.org/10.1007/s10689-011-9468-4
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DOI: https://doi.org/10.1007/s10689-011-9468-4