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Published in: International Journal of Colorectal Disease 5/2005

01-09-2005 | Case Report

Double frameshift mutations in APC and MSH2 in the same individual

Authors: Claudio Soravia, Celia D. DeLozier, Zuzana Dobbie, Claudine Rey Berthod, Eviano Arrigoni, Marie-Anne Bründler, Jean-Louis Blouin, William D. Foulkes, Pierre Hutter

Published in: International Journal of Colorectal Disease | Issue 5/2005

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Abstract

Heterozygous germline DNA mismatch repair gene mutations are typically associated with HNPCC. Here we report the case of a proband whose father was known for familial adenomatous polyposis. The number of polyps (<10) was not typical of polyposis, therefore the diagnosis of HNPCC was entertained. Microsatellite instability analyses were performed on peripheral blood and biopsy of a right-sided dysplastic adenoma. The tumour tissue showed high-grade instability and subsequently immunohistochemistry showed that neither MSH2 nor MSH6 proteins were expressed in tumour cells. Prophylactic colectomy was performed and an adenocarcinoma developing within the adenoma was diagnosed (pT1N0). Genomic DNA analysis revealed a novel mutation in MSH2 as: a frameshift mutation in exon 7 (c.1,191_1,192dupG). Both parents of the proband were analyzed for MSH2 and APC mutations, and in the father a truncating mutation in exon 15 of APC was identified as del3471-3473GAGA. This mutation was found to be present in the proband. His mother was found to bear the MSH2 exon 7 mutation. At follow-up, the proband was diagnosed with fundic, antral and duodenal adenomas (one fundic adenoma showed low-grade dysplasia). Several tubular rectal adenomas with low-grade dysplasia were excised. The patient later developed an intra-abdominal desmoid tumour.
Literature
1.
go back to reference Altonen LA, Salovaara R, Kristo P et al (1998) Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease. N Engl J Med 338:1481–1487CrossRefPubMed Altonen LA, Salovaara R, Kristo P et al (1998) Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease. N Engl J Med 338:1481–1487CrossRefPubMed
2.
go back to reference Lynch HT, de la Chapelle A (2003) Hereditary colorectal cancer. N Engl J Med 348:919–932CrossRef Lynch HT, de la Chapelle A (2003) Hereditary colorectal cancer. N Engl J Med 348:919–932CrossRef
3.
go back to reference Soravia C, Cohen Z (2005) Familial adenomatous polyposis. In: Fazio VW, Church JM, Delaney CP (eds) Current therapy in colon and rectal surgery. Elsevier Mosby, Philadelphia, pp 349–353 Soravia C, Cohen Z (2005) Familial adenomatous polyposis. In: Fazio VW, Church JM, Delaney CP (eds) Current therapy in colon and rectal surgery. Elsevier Mosby, Philadelphia, pp 349–353
4.
go back to reference Kariola R, Otway R, Lonnqvist KE et al (2003) Two mismatch repair gene mutations found in a colon cancer patient—which one is pathogenic? Hum Genet 112(2):105–109 Kariola R, Otway R, Lonnqvist KE et al (2003) Two mismatch repair gene mutations found in a colon cancer patient—which one is pathogenic? Hum Genet 112(2):105–109
5.
go back to reference Whiteside D, McLeod R, Graham G et al (2002) A homozygous germ-line mutation in the human MSH2 gene predisposes to hematological malignancy and multiple café-au-lait spots. Cancer Res 62:359–362PubMed Whiteside D, McLeod R, Graham G et al (2002) A homozygous germ-line mutation in the human MSH2 gene predisposes to hematological malignancy and multiple café-au-lait spots. Cancer Res 62:359–362PubMed
6.
go back to reference Gallinger S, Aronson M, Shayan K et al (2004) Gastrointestinal cancers and neurofibromatosis type 1 features in children with a germline homozygous MLH1 mutation. Gastroenterology 126:576–585 Gallinger S, Aronson M, Shayan K et al (2004) Gastrointestinal cancers and neurofibromatosis type 1 features in children with a germline homozygous MLH1 mutation. Gastroenterology 126:576–585
7.
go back to reference Yuan ZQ, Kasprzak L, Gordon PH, Pinsky L, Foulkes WD (1998) I1307K APC and hMLH1 mutations in a non-Jewish family with hereditary non-polyposis colorectal cancer. Clin Genet 54:369–370 Yuan ZQ, Kasprzak L, Gordon PH, Pinsky L, Foulkes WD (1998) I1307K APC and hMLH1 mutations in a non-Jewish family with hereditary non-polyposis colorectal cancer. Clin Genet 54:369–370
8.
go back to reference Yuan ZQ, Wong N, Foulkes WD et al (1999) A missense mutation in both hMSH2 and APC in an Ashkenazi Jewish HNPCC kindred: implications for clinical screening. J Med Genet 36:790–793 Yuan ZQ, Wong N, Foulkes WD et al (1999) A missense mutation in both hMSH2 and APC in an Ashkenazi Jewish HNPCC kindred: implications for clinical screening. J Med Genet 36:790–793
9.
go back to reference Scheenstra R, Rijcken FE, Koornstra JJ et al (2003) Rapidly progressive adenomatous polyposis in a patient with germline mutations in both the APC and MLH1 genes: the worst of two worlds. Gut 52:898–899 Scheenstra R, Rijcken FE, Koornstra JJ et al (2003) Rapidly progressive adenomatous polyposis in a patient with germline mutations in both the APC and MLH1 genes: the worst of two worlds. Gut 52:898–899
10.
go back to reference Soravia C, Berk T, Madlensky L et al (1998) Genotype–phenotype correlations in attenuated adenomatous polyposis coli. Am J Hum Genet 62:1290–1301PubMed Soravia C, Berk T, Madlensky L et al (1998) Genotype–phenotype correlations in attenuated adenomatous polyposis coli. Am J Hum Genet 62:1290–1301PubMed
11.
go back to reference Cao Y, Pieretti M, Marshall J, Khattar NH, Chen B, Kam-Morgan L, Lynch H (2002) Challenge in the differentiation between attenuated familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer: case report with review of the literature. Am J Gastroenterol 97(7):182 Cao Y, Pieretti M, Marshall J, Khattar NH, Chen B, Kam-Morgan L, Lynch H (2002) Challenge in the differentiation between attenuated familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer: case report with review of the literature. Am J Gastroenterol 97(7):182
12.
go back to reference Soravia C, Berk T, McLeod RS, Cohen Z (2000) Desmoid disease in patients with familial adenomatous polyposis (FAP). Dis Colon Rectum 43:363–369 Soravia C, Berk T, McLeod RS, Cohen Z (2000) Desmoid disease in patients with familial adenomatous polyposis (FAP). Dis Colon Rectum 43:363–369
13.
go back to reference Davies DR, Armstrong JG, Thakker N et al (1995) Severe Gardner syndrome in families with mutations restricted to a specific region of the APC gene. Am J Hum Genet 57:1151–1158 Davies DR, Armstrong JG, Thakker N et al (1995) Severe Gardner syndrome in families with mutations restricted to a specific region of the APC gene. Am J Hum Genet 57:1151–1158
14.
go back to reference Caspari R, Olschwang S, Friedl W et al (1995) Familial adenomatous polyposis: desmoid tumours and lack of ophthalmic lesions (CHRPE) associated with APC mutations beyond codon 1444. Hum Mol Genet 4:337–340 Caspari R, Olschwang S, Friedl W et al (1995) Familial adenomatous polyposis: desmoid tumours and lack of ophthalmic lesions (CHRPE) associated with APC mutations beyond codon 1444. Hum Mol Genet 4:337–340
15.
go back to reference 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 21:1698–1707CrossRefPubMed 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 21:1698–1707CrossRefPubMed
16.
go back to reference Aarnio M, Salovaara R, Aaltonen LA, Mecklin JP, Järvinen H (1997) Features of gastric cancer in hereditary non-polyposis colorectal cancer syndrome. Int J Cancer 74:551–555 Aarnio M, Salovaara R, Aaltonen LA, Mecklin JP, Järvinen H (1997) Features of gastric cancer in hereditary non-polyposis colorectal cancer syndrome. Int J Cancer 74:551–555
17.
go back to reference Nakamura S, Matsumoto T, Kobori Y, Iida M (2002) Impact of Helicobacter pylori infection and mucosal atrophy on gastric lesions in patients with familial adenomatous polyposis. Gut 51:485–489 Nakamura S, Matsumoto T, Kobori Y, Iida M (2002) Impact of Helicobacter pylori infection and mucosal atrophy on gastric lesions in patients with familial adenomatous polyposis. Gut 51:485–489
18.
go back to reference Zajac V, Tompka M, Ilencikova D, Majek P, Stevurkova V, Kirchoff T (2000) A double germline mutations in the APC and p53 genes. Neoplasma 47(6):335–341 Zajac V, Tompka M, Ilencikova D, Majek P, Stevurkova V, Kirchoff T (2000) A double germline mutations in the APC and p53 genes. Neoplasma 47(6):335–341
19.
go back to reference Edelmann W, Yang K, Kuraguchi M et al (1999) Tumorigenesis in Mlh1 and Mlh1/Apc1638N mutant mice. Cancer Res 59:1301–1307 Edelmann W, Yang K, Kuraguchi M et al (1999) Tumorigenesis in Mlh1 and Mlh1/Apc1638N mutant mice. Cancer Res 59:1301–1307
20.
go back to reference Shoemaker AR, Haigis KM, Baker SM et al (2000) Mlh1 deficiency enhances several phenotypes of Apc(Min)/+ mice. Oncogene 19:2774–2779 Shoemaker AR, Haigis KM, Baker SM et al (2000) Mlh1 deficiency enhances several phenotypes of Apc(Min)/+ mice. Oncogene 19:2774–2779
21.
go back to reference Niell BL, Long JC, Rennert G, Gruber SB (2003) Genetic anthropology of the colorectal cancer-susceptibility allele APC I1307K: evidence of genetic drift within the Ashkenazim. Am J Hum Genet 73:1250–1260 Niell BL, Long JC, Rennert G, Gruber SB (2003) Genetic anthropology of the colorectal cancer-susceptibility allele APC I1307K: evidence of genetic drift within the Ashkenazim. Am J Hum Genet 73:1250–1260
22.
go back to reference Foulkes WD, Thiffault I, Gruber SB et al (2002) The founder mutation MSH2*1906G->C is an important cause of hereditary nonpolyposis colorectal cancer in the Ashkenazi Jewish population. Am J Hum Genet 71:1395–1412 Foulkes WD, Thiffault I, Gruber SB et al (2002) The founder mutation MSH2*1906G->C is an important cause of hereditary nonpolyposis colorectal cancer in the Ashkenazi Jewish population. Am J Hum Genet 71:1395–1412
23.
24.
go back to reference Yuen ST, Chan TL, Ho JW et al (2002) Germline, somatic and epigenetic events underlying mismatch repair deficiency in colorectal and HNPCC-related cancers. Oncogene 21(49):7585–7592 Yuen ST, Chan TL, Ho JW et al (2002) Germline, somatic and epigenetic events underlying mismatch repair deficiency in colorectal and HNPCC-related cancers. Oncogene 21(49):7585–7592
25.
go back to reference Jass JJ, Whitehall VLJ, Young J, Legget BA (2002) Emerging concepts in colorectal neoplasia. Gastroenterology 123:862–876 Jass JJ, Whitehall VLJ, Young J, Legget BA (2002) Emerging concepts in colorectal neoplasia. Gastroenterology 123:862–876
26.
go back to reference Mirabelli-Primdahl L, Gryfe R, Kim H et al (1999) Beta-catenin mutations are specific for colorectal carcinomas with microsatellite instability but occur in endometrial carcinomas irrespective of mutator pathway. Cancer Res 59:3346–3351 Mirabelli-Primdahl L, Gryfe R, Kim H et al (1999) Beta-catenin mutations are specific for colorectal carcinomas with microsatellite instability but occur in endometrial carcinomas irrespective of mutator pathway. Cancer Res 59:3346–3351
Metadata
Title
Double frameshift mutations in APC and MSH2 in the same individual
Authors
Claudio Soravia
Celia D. DeLozier
Zuzana Dobbie
Claudine Rey Berthod
Eviano Arrigoni
Marie-Anne Bründler
Jean-Louis Blouin
William D. Foulkes
Pierre Hutter
Publication date
01-09-2005
Publisher
Springer-Verlag
Published in
International Journal of Colorectal Disease / Issue 5/2005
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI
https://doi.org/10.1007/s00384-005-0764-z

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