Genetic testing for germline mutations of the APC gene in patients with apparently sporadic desmoid tumors but a family history of colorectal carcinoma

Wolfgang M. Brueckl, Wolfgang G. Ballhausen, Thomas Förtsch, Klaus Günther, Wolfgang Fiedler, Bernhard Gentner, Roland Croner, Frank Boxberger, Thomas Kirchner, Eckhart G. Hahn, Werner Hohenberger, Axel Wein

Research output: Contribution to journalArticle

Abstract

PURPOSE: Desmoid tumors, also known as aggressive fibromatosis, occur with an incidence of 10 to 15 percent in patients affected by familial adenomatous polyposis, an autosomal inherited disease caused by germline mutations in the APC gene. However, sporadic forms with no hereditary background exist. The aim of this study was to find out whether there are APC germline mutations in apparently sporadic desmoid tumor patients without clinical or familial signs of familial adenomatous polyposis but with a family history of colorectal carcinoma in at least one family member. METHODS: Genomic DNA and mRNA were isolated from peripheral blood leukocytes of index patients of eight nonrelated families. Mutation screening was performed using reverse transcriptase polymerase chain reaction-based protein truncation test for APC exons 1-14. The large APC exon 15 was scrutinized by the protein truncation test of four overlapping genomic fragments. Additionally, genomic DNA from five desmoid tumors was analyzed for loss of heterozygosity at D5S346 close to the APC locus. RESULTS: No translational stop mutations typical for familial adenomatous polyposis could be found in the APC gene in any of the analyzed blood samples from the desmoid tumor patients. Additionally, no loss of heterozygosity at D5S346 was found in four of five desmoids; one tumor was not informative. CONCLUSIONS: These results may suggest that patients with sporadic desmoids and no clinical signs of familial adenomatous polyposis detected on careful examination, esophagogastroduodenoscopy, and complete colonoscopy do not need to be tested routinely for germline mutations of the APC gene. However, as large studies dealing with this problem are absent, it might be more time and cost effective to perform an APC mutational analysis instead.

Original languageEnglish
Pages (from-to)1275-1281
Number of pages7
JournalDiseases of the Colon and Rectum
Volume48
Issue number6
DOIs
Publication statusPublished - Jun 2005

Fingerprint

APC Genes
Aggressive Fibromatosis
Germ-Line Mutation
Genetic Testing
Colorectal Neoplasms
Adenomatous Polyposis Coli
Neoplasms
Loss of Heterozygosity
Exons
Digestive System Endoscopy
Mutation
DNA
Colonoscopy
Reverse Transcriptase Polymerase Chain Reaction
Proteins
Leukocytes
Costs and Cost Analysis
Messenger RNA
Incidence

Keywords

  • Adenomatous poly-posis coli
  • Desmoid tumor
  • Familial adenomatous polyposis
  • Germline mutation

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Genetic testing for germline mutations of the APC gene in patients with apparently sporadic desmoid tumors but a family history of colorectal carcinoma. / Brueckl, Wolfgang M.; Ballhausen, Wolfgang G.; Förtsch, Thomas; Günther, Klaus; Fiedler, Wolfgang; Gentner, Bernhard; Croner, Roland; Boxberger, Frank; Kirchner, Thomas; Hahn, Eckhart G.; Hohenberger, Werner; Wein, Axel.

In: Diseases of the Colon and Rectum, Vol. 48, No. 6, 06.2005, p. 1275-1281.

Research output: Contribution to journalArticle

Brueckl, WM, Ballhausen, WG, Förtsch, T, Günther, K, Fiedler, W, Gentner, B, Croner, R, Boxberger, F, Kirchner, T, Hahn, EG, Hohenberger, W & Wein, A 2005, 'Genetic testing for germline mutations of the APC gene in patients with apparently sporadic desmoid tumors but a family history of colorectal carcinoma', Diseases of the Colon and Rectum, vol. 48, no. 6, pp. 1275-1281. https://doi.org/10.1007/s10350-004-0949-5
Brueckl, Wolfgang M. ; Ballhausen, Wolfgang G. ; Förtsch, Thomas ; Günther, Klaus ; Fiedler, Wolfgang ; Gentner, Bernhard ; Croner, Roland ; Boxberger, Frank ; Kirchner, Thomas ; Hahn, Eckhart G. ; Hohenberger, Werner ; Wein, Axel. / Genetic testing for germline mutations of the APC gene in patients with apparently sporadic desmoid tumors but a family history of colorectal carcinoma. In: Diseases of the Colon and Rectum. 2005 ; Vol. 48, No. 6. pp. 1275-1281.
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abstract = "PURPOSE: Desmoid tumors, also known as aggressive fibromatosis, occur with an incidence of 10 to 15 percent in patients affected by familial adenomatous polyposis, an autosomal inherited disease caused by germline mutations in the APC gene. However, sporadic forms with no hereditary background exist. The aim of this study was to find out whether there are APC germline mutations in apparently sporadic desmoid tumor patients without clinical or familial signs of familial adenomatous polyposis but with a family history of colorectal carcinoma in at least one family member. METHODS: Genomic DNA and mRNA were isolated from peripheral blood leukocytes of index patients of eight nonrelated families. Mutation screening was performed using reverse transcriptase polymerase chain reaction-based protein truncation test for APC exons 1-14. The large APC exon 15 was scrutinized by the protein truncation test of four overlapping genomic fragments. Additionally, genomic DNA from five desmoid tumors was analyzed for loss of heterozygosity at D5S346 close to the APC locus. RESULTS: No translational stop mutations typical for familial adenomatous polyposis could be found in the APC gene in any of the analyzed blood samples from the desmoid tumor patients. Additionally, no loss of heterozygosity at D5S346 was found in four of five desmoids; one tumor was not informative. CONCLUSIONS: These results may suggest that patients with sporadic desmoids and no clinical signs of familial adenomatous polyposis detected on careful examination, esophagogastroduodenoscopy, and complete colonoscopy do not need to be tested routinely for germline mutations of the APC gene. However, as large studies dealing with this problem are absent, it might be more time and cost effective to perform an APC mutational analysis instead.",
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T1 - Genetic testing for germline mutations of the APC gene in patients with apparently sporadic desmoid tumors but a family history of colorectal carcinoma

AU - Brueckl, Wolfgang M.

AU - Ballhausen, Wolfgang G.

AU - Förtsch, Thomas

AU - Günther, Klaus

AU - Fiedler, Wolfgang

AU - Gentner, Bernhard

AU - Croner, Roland

AU - Boxberger, Frank

AU - Kirchner, Thomas

AU - Hahn, Eckhart G.

AU - Hohenberger, Werner

AU - Wein, Axel

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N2 - PURPOSE: Desmoid tumors, also known as aggressive fibromatosis, occur with an incidence of 10 to 15 percent in patients affected by familial adenomatous polyposis, an autosomal inherited disease caused by germline mutations in the APC gene. However, sporadic forms with no hereditary background exist. The aim of this study was to find out whether there are APC germline mutations in apparently sporadic desmoid tumor patients without clinical or familial signs of familial adenomatous polyposis but with a family history of colorectal carcinoma in at least one family member. METHODS: Genomic DNA and mRNA were isolated from peripheral blood leukocytes of index patients of eight nonrelated families. Mutation screening was performed using reverse transcriptase polymerase chain reaction-based protein truncation test for APC exons 1-14. The large APC exon 15 was scrutinized by the protein truncation test of four overlapping genomic fragments. Additionally, genomic DNA from five desmoid tumors was analyzed for loss of heterozygosity at D5S346 close to the APC locus. RESULTS: No translational stop mutations typical for familial adenomatous polyposis could be found in the APC gene in any of the analyzed blood samples from the desmoid tumor patients. Additionally, no loss of heterozygosity at D5S346 was found in four of five desmoids; one tumor was not informative. CONCLUSIONS: These results may suggest that patients with sporadic desmoids and no clinical signs of familial adenomatous polyposis detected on careful examination, esophagogastroduodenoscopy, and complete colonoscopy do not need to be tested routinely for germline mutations of the APC gene. However, as large studies dealing with this problem are absent, it might be more time and cost effective to perform an APC mutational analysis instead.

AB - PURPOSE: Desmoid tumors, also known as aggressive fibromatosis, occur with an incidence of 10 to 15 percent in patients affected by familial adenomatous polyposis, an autosomal inherited disease caused by germline mutations in the APC gene. However, sporadic forms with no hereditary background exist. The aim of this study was to find out whether there are APC germline mutations in apparently sporadic desmoid tumor patients without clinical or familial signs of familial adenomatous polyposis but with a family history of colorectal carcinoma in at least one family member. METHODS: Genomic DNA and mRNA were isolated from peripheral blood leukocytes of index patients of eight nonrelated families. Mutation screening was performed using reverse transcriptase polymerase chain reaction-based protein truncation test for APC exons 1-14. The large APC exon 15 was scrutinized by the protein truncation test of four overlapping genomic fragments. Additionally, genomic DNA from five desmoid tumors was analyzed for loss of heterozygosity at D5S346 close to the APC locus. RESULTS: No translational stop mutations typical for familial adenomatous polyposis could be found in the APC gene in any of the analyzed blood samples from the desmoid tumor patients. Additionally, no loss of heterozygosity at D5S346 was found in four of five desmoids; one tumor was not informative. CONCLUSIONS: These results may suggest that patients with sporadic desmoids and no clinical signs of familial adenomatous polyposis detected on careful examination, esophagogastroduodenoscopy, and complete colonoscopy do not need to be tested routinely for germline mutations of the APC gene. However, as large studies dealing with this problem are absent, it might be more time and cost effective to perform an APC mutational analysis instead.

KW - Adenomatous poly-posis coli

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KW - Familial adenomatous polyposis

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