Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Diseases of the Colon & Rectum
Published in: Diseases of the Colon & Rectum 11/2007

01-11-2007 | Original Contributions

The Mutation Spectrum of the APC Gene in Turkish Patients with Familial Adenomatous Polyposis

Authors: Berrin Tunca, Ph.D., Gulsah Cecener, Ph.D., Unal Egeli, Ph.D., Abdullah Zorluoglu, M.D., Tuncay Yilmazlar, M.D.

Published in: Diseases of the Colon & Rectum | Issue 11/2007

Login to get access

Abstract

Purpose

Familial adenomatous polyposis, an autosomal-dominant disease characterized by the presence of 100 or more colorectal adenomatous polyps, results from mutations in the adenomatous polyposis coli tumor suppressor gene. This study was designed to investigate adenomatous polyposis coli gene mutations in members of Turkish families with familial adenomatous polyposis to constitute an adenomatous polyposis coli mutation spectrum for the Turkish population and to determine specific biomarkers for use in the early diagnosis of familial adenomatous polyposis.

Methods

We investigated adenomatous polyposis coli gene mutations in six unrelated families with familial adenomatous polyposis by using heteroduplex analysis and DNA sequencing.

Results

We identified three different mutations in six families. Of these one is known and two are novel: 1018T>C and 1309delGAAAA. The mutation of a T to C transversion at codon 1018 does not cause an alteration in the meaning of the codon; however, it was determined that this silent mutation does cause the formation of new exonic splicing enhancers (ESEs) motifs on a mutated sequence by using ESEfinder program.

Conclusions

This study contributes to enlarging the adenomatous polyposis coli gene mutations spectrum and to defining new biomarkers for the early diagnosis of Turkish patients with familial adenomatous polyposis.
Literature
1.
2.
Tunca B, Menigatti M, Benatti P, et al. Investigation of APC mutations in a Turkish familial adenomatous polyposis family by heterodublex analysis. Dis Colon Rectum 2005;48:567-1.CrossRefPubMed
3.
4.
Kinzler KW, Nilbert MC, Vogelstein B, et al. Identification of a gene located at chromosome 5q21 that is mutated in colorectal cancers. Science 1991;251:1366-0.CrossRefPubMed
5.
Groden J, Thliveris A, Samowitz W, et al. Identification and characterization of the familial adenomatous polyposis coli gene. Cell 1991;66:589–600.CrossRefPubMed
6.
Aretz S, Uhlhaas S, Sun Y, et al. Familial adenomatous polyposis: aberrant splicing due to missense or silent mutations in the APC gene. Human Mutation 2004;24:370-0.CrossRefPubMed
7.
Cartegni L, Wang J, Zhu Z, et al. ESEfinder: a web resource to identify exonic splicing enhancers. Nucleic Acid Res 2003;31:3568-1.CrossRefPubMed
8.
Miyoshi Y, Ando H, Nagase H, et al. Germ-line mutations of the APC gene in 53 familial adenomatous polyposis patients. Proc Natl Acad Sci USA 1992;89:4452-CrossRefPubMed
9.
Wang J, Smith PJ, Krainer AR, Zang MQ. Distribution of SR protein exonic splicing enhancer motifs human protein-coding genes. Nucleic Acids Res 2005;33:5053-2.CrossRefPubMed
10.
Nishisho I, Nakamura Y, Miyoshi Y, et al. Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science 1991;253:665-.CrossRefPubMed
11.
Dobbie Z, Spycher M, Hurliman R, et al. Mutational analysis of the first 14 exons of the adenomatous polyposis coli (APC) gene. Eur J Cancer 1994;30A:1709-3CrossRefPubMed
12.
van der Luijt RB, Khan PM, Vasen HF, et al. Molecular analysis of the APC gene in 105 Dutch kindreds with familial adenomatous polyposis: 67 germline mutations identified by DGGE, PTT, and Southern analysis. Hum Mutat 1997;9:7–16.CrossRefPubMed
13.
Laken SJ, Petersen GM, Gruber SB, et al. Familial colorectal cancer in Ashkenazim due to a hypermutable tract in APC. Nat Genet 1997;17:79–83.CrossRefPubMed
14.
van der Luijt RB, Meera Khan P, Vasen HF, et al. Germline mutations in the 30 part of APC exon 15 do not result in truncated proteins and are associated with attenuated adenomatous polyposis coli. Hum Genet 1996;98:727-4.CrossRefPubMed
15.
Frayling IM, Beck NE, Ilyas M, et al. The APC variants I1307K and E1317Q are associated with colorectal tumors, but not always with a family history. Proc Natl Acad Sci USA 1998;95:10722-.CrossRefPubMed
16.
Ficari F, Cama A, Valanzano R, et al. APC gene mutations and colorectal adenomatosis in familial adenomatous polyposis. Br J Cancer 2000;82:348-3.CrossRefPubMed
17.
Montera M, Piaggio F, Marchese C, et al. A silent mutation in exon 14 of the APC gene is associated with exon skipping in a FAP family. J Med Genet 2001;38:863-CrossRefPubMed
18.
Fackenthal JD, Cartegni L, Krainer AR, Olopade OI. BRCA2 T2722R is a deleterious allele that causes exon skipping. Am J Hum Genet 2002;71:625-1.CrossRefPubMed
19.
Yang Y, Swaminathan S, Martin BK, Sharan SK. Aberrant splicing induced by missense mutations in BRCA1: clues from a humanized mouse model. Hum Mol Genet 2003;12:2121-1.CrossRefPubMed
20.
Cartegni L, Chew SL, Krainer AR. Listening to silence and understanding nonsense: exonic mutations that affect splicing. Nat Rev Genet 2002;3:285-8.CrossRefPubMed
21.
Fu XD. The superfamily of arginine/serine-rich splicing factors. RNA 1995;1:663-0.PubMed
22.
Valcarcel J, Green MR. The SR protein family: pleiotropic functions in pre-mRNA splicing. Trends Biochem Sci 1996;21:296–301.PubMed
23.
Liu HX, Zhang M, Krainer AR. Identification of functional exonic splicing enhancer motifs recognized by individual SR proteins. Genes Dev 1998;12:1998–2012.CrossRefPubMed
24.
Liu HX, Chew SL, Cartegni L, et al. Exonic splicing enhancer motif recognized by human SC35 under splicing conditions. Mol Cell Biol 2000;20:1063-1.CrossRefPubMed
Metadata
Title
The Mutation Spectrum of the APC Gene in Turkish Patients with Familial Adenomatous Polyposis
Authors
Berrin Tunca, Ph.D.
Gulsah Cecener, Ph.D.
Unal Egeli, Ph.D.
Abdullah Zorluoglu, M.D.
Tuncay Yilmazlar, M.D.
Publication date
01-11-2007
Publisher
Springer-Verlag
Published in
Diseases of the Colon & Rectum / Issue 11/2007
Print ISSN: 0012-3706
Electronic ISSN: 1530-0358
DOI
https://doi.org/10.1007/s10350-007-9056-8

Other articles of this Issue 11/2007

Diseases of the Colon & Rectum 11/2007 Go to the issue

Original Contributions

Clinical Entity and Treatment Strategies for Adult Intussusceptions: 20 Years-Experience

Announcement

Self-Assessment Quiz: Answers, Critiques, and References

Original Contributions

Multivariate Analysis of Predictive Factors for Early Postoperative Death After Colorectal Surgery in Patients with Colorectal Cancer and Synchronous Unresectable Liver Metastases

Original Contributions

Dartos Muscle Interposition Flap for the Treatment of Rectourethral Fistulas

Book Reviews

Sleisenger and Fordtran’s Gastrointestinal and Liver Disease. 8th ed. Pathophysiology/Diagnosis/Management.

Original Contributions

Four Percent of Patients Undergoing Colorectal Cancer Surgery may have Synchronous Appendiceal Neoplasia