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01-10-2007 | Original Contributions

Colorectal Adenomatous Polyposis Associated with MYH Mutations: Genotype and Phenotype Characteristics

Authors: Guillaume Bouguen, M.S., Sylvain Manfredi, M.D., Martine Blayau, M.D., Catherine Dugast, M.D., Bruno Buecher, M.D., Dominique Bonneau, Ph.D., Laurent Siproudhis, Ph.D., Véronique David, Ph.D., Jean-François Bretagne, Ph.D.

Published in: Diseases of the Colon & Rectum | Issue 10/2007

Abstract

Purpose

Recent literature reports that several digestive diseases are associated with mutations in the base excision repair gene MYH. This study was designed to establish the prevalence of germ-line MYH mutations in a series of 56 consecutive patients with no detectable APC mutation and describe the phenotype of those with MYH mutations.

Methods

MYH mutations were screened by DNA sequencing after polymerase chain reaction amplification of each exon. Clinical, endoscopic, and surgical data were collected for the tested patients.

Results

MYH mutations were identified only in the group of patients with attenuated adenomatous polyposis with ten or more adenomatous polyps. The prevalence of MYH mutations was 34.4 percent (11 cases) in this subgroup of 30 patients. There were two homozygotes and eight compound heterozygotes. Only one patient had a monoallelic mutation. At least one of two mutational hot spots was identified in ten patients. Three patients presented with a family history of adenomatous polyposis in siblings, without vertical transmission. The median number of colorectal adenomatous polyps was 53 without preferential localization. Colorectal cancer was associated with polyposis in seven patients. Gastric and duodenal adenomas were diagnosed in one case. Ten of 11 patients underwent colectomy.

Conclusions

MYH mutations have been observed in one-third of patients with attenuated polyposis. The phenotype of the disease is similar to attenuated familial adenomatous polyposis. Upper gastrointestinal endoscopy also should be recommended. However, its transmission shows evidence of a recessive pattern.

Venesio T, Molatore S, Cattaneo F, et al. High frequency of MYH gene mutations in a subset of patients with familial adenomatous polyposis. Gastroenterology 2004;126:1681–5.PubMedCrossRef

Spirio L, Olschwang S, Groden J, et al. Alleles of the APC gene: an attenuated form of familial polyposis. Cell 1993;75:951–7.PubMedCrossRef

Lamlum H, Al Tassan N, Jaeger E, et al. Germline APC variants in patients with multiple colorectal adenomas, with evidence for the particular importance of E1317Q. Hum Mol Genet 2000;9:2215–21.PubMed

Heinimann K, Thompson A, Locher A, et al. Nontruncating APC germ-line mutations and mismatch repair deficiency play a minor role in APC mutation-negative polyposis. Cancer Res 2001;61:7616–22.PubMed

Sakumi K, Furuichi M, Tsuzuki T, et al. Cloning and expression of cDNA for a human enzyme that hydrolyzes 8-oxo-dGTP, a mutagenic substrate for DNA synthesis. J Biol Chem 1993;268:23524–30.PubMed

Roldan-Arjona T, Wei YF, Carter KC, et al. Molecular cloning and functional expression of a human cDNA encoding the antimutator enzyme 8-hydroxyguanine-DNA glycosylase. Proc Natl Acad Sci U S A 1997;94:8016–20.PubMedCrossRef

Slupska MM, Baikalov C, Luther WM, et al. Cloning and sequencing a human homolog (hMYH) of the Escherichia coli mutY gene whose function is required for the repair of oxidative DNA damage. J Bacteriol 1996;178:3885–92.PubMed

Sieber OM, Lipton L, Crabtree M, et al. Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH. N Engl J Med 2003;348:791–9.PubMedCrossRef

Kim IJ, Ku JL, Kang HC, et al. Mutational analysis of OGG1, MYH, MTH1 in FAP, HNPCC and sporadic colorectal cancer patients: R154H OGG1 polymorphism is associated with sporadic colorectal cancer patients. Hum Genet 2004;115:498–503.PubMedCrossRef

10.

Halford SE, Rowan AJ, Lipton L, et al. Germline mutations but not somatic changes at the MYH locus contribute to the pathogenesis of unselected colorectal cancers. Am J Pathol 2003;162:1545–8.PubMed

11.

Al-Tassan N, Chmiel NH, Maynard J, et al. Inherited variants of MYH associated with somatic G:C->T:A mutations in colorectal tumors. Nat Genet 2002;30:227–32.PubMedCrossRef

12.

Chmiel NH, Livingston AL, David SS. Insight into the functional consequences of inherited variants of the hMYH adenine glycosylase associated with colorectal cancer: complementation assays with hMYH variants and pre-steady-state kinetics of the corresponding mutated E. coli enzymes. J Mol Biol 2003;327:431–43.PubMedCrossRef

13.

Fleischmann C, Peto J, Cheadle J, et al. Comprehensive analysis of the contribution of germline MYH variation to early-onset colorectal cancer. Int J Cancer 2004;20:554–8.CrossRef

14.

Kairupan CF, Meldrum CJ, Crooks R, et al. Mutation analysis of the MYH gene in an Australian series of colorectal polyposis patients with or without germline APC mutations. Int J Cancer 2005;116:73–7.PubMedCrossRef

15.

Nielsen M, Franken PF, Reinards TH, et al. Multiplicity in polyp count and extracolonic manifestations in 40 Dutch patients with MYH associated polyposis coli (MAP). J Med Genet 2005;42:54–7.CrossRef

16.

Russell AM, Zhang J, Luz J, et al. Prevalence of MYH germline mutations in Swiss APC mutation-negative polyposis patients. Int J Cancer 2006;118:1937–40.PubMedCrossRef

17.

Wang L, Baudhuin LM, Boardman LA, et al. MYH mutations in patients with attenuated and classic polyposis and with young-onset colorectal cancer without polyps. Gastroenterology 2004;127:9–16.PubMedCrossRef

18.

Sampson JR, Dolwani S, Jones S, et al. Autosomal recessive colorectal adenomatous polyposis due to inherited mutations of MYH. Lancet 2003;362:39–41.PubMedCrossRef

19.

Jenkins MA, Croitoru ME, Monga N, et al. Risk of colorectal cancer in monoallelic and biallelic carriers of MYH mutations: a population-based case-family study. Cancer Epidemiol Biomarkers Prev 2006;15:312–4.PubMedCrossRef

20.

Truta B, Allen BA, Conrad PG, et al. A comparison of the phenotype and genotype in adenomatous polyposis patients with and without a family history. Fam Cancer 2005;4:127–33.PubMedCrossRef

21.

Enholm S, Hienonen T, Suomalainen A, et al. Proportion and phenotype of MYH-associated colorectal neoplasia in a population-based series of Finnish colorectal cancer patients. Am J Pathol 2003;163:827–32.PubMed

22.

Hemminki K, Chen B. Familial risks for colorectal cancer show evidence on recessive inheritance. Int J Cancer 2005;115:835–8.PubMedCrossRef

23.

Fornasarig M, Minisini AM, Viel A, et al. Twelve years of endoscopic surveillance in a family carrying biallelic Y165C MYH defect: report of a case. Dis Colon Rectum 2006;49:272–5.PubMedCrossRef

24.

Leite JS, Isidro G, Martins M, et al. Is prophylactic colectomy indicated in patients with MYH-associated polyposis? Colorectal Dis 2005;7:327–31.PubMedCrossRef

25.

Sobin LH, Fleming ID. TNM classification of malignant tumors. 5th ed. Union Internationale Contre le Cancer and the American Joint Committee on Cancer. Cancer 1997;80:1803–4.PubMedCrossRef

Title: Colorectal Adenomatous Polyposis Associated with MYH Mutations: Genotype and Phenotype Characteristics
Authors: Guillaume Bouguen, M.S.
Sylvain Manfredi, M.D.
Martine Blayau, M.D.
Catherine Dugast, M.D.
Bruno Buecher, M.D.
Dominique Bonneau, Ph.D.
Laurent Siproudhis, Ph.D.
Véronique David, Ph.D.
Jean-François Bretagne, Ph.D.
Publication date: 01-10-2007
Publisher: Springer-Verlag
Published in: Diseases of the Colon & Rectum / Issue 10/2007
Print ISSN: 0012-3706
Electronic ISSN: 1530-0358
DOI: https://doi.org/10.1007/s10350-007-9027-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Colorectal Adenomatous Polyposis Associated with MYH Mutations: Genotype and Phenotype Characteristics

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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