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Mutational screening of the APC gene in Chilean families with familial adenomatous polyposis: nine novel truncating mutations.
Dis Colon Rectum. 2007 Dec; 50(12):2142-8.DC

Abstract

PURPOSE

Familial adenomatous polyposis is characterized by the development of hundreds of adenomatous polyps located mainly in the colon and rectum. Patients with familial adenomatous polyposis who do not receive treatment will develop cancer before aged 40 years. This disease is caused by germline mutations in the adenomatous polyposis coli gene. Different studies have shown a correlation between the location of the mutation and the clinical phenotype, such as the grade of severity and/or the presence of extracolonic manifestations, such as desmoid tumors. This study was designed to identify germline mutation in the adenomatous polyposis coli gene in Chilean families with familial adenomatous polyposis.

METHODS

We examined the adenomatous polyposis coli gene in 24 Chilean families with familial adenomatous polyposis. The adenomatous polyposis coli gene was screened for mutations combining single strand conformation polymorphism technique, protein truncation test, and DNA sequencing.

RESULTS

We detected 17 different truncating mutations in 21 of 24 families (87.5 percent); 9 of these were novel. Fourteen mutations were detected in exon 15, being the most frequent c.3,927_3,931delAAAGA, found in 3 of 21 families (14 percent). Eight families (33 percent) showed at least one patient affected with desmoid tumors, presenting mutations between codons 849 and 1,533. Interestingly, two mutations, c.3,632dupA and c.3,783_3,784delTT, leading into a truncating protein at codons 1,216 and 1,274, were associated with almost 100 percent penetrance for desmoid tumors among relatives.

CONCLUSIONS

We achieved 87 percent mutation detection rate in adenomatous polyposis coli gene; more than 50 percent of them were novel. The high percentage of novel mutations found may be because of the genetic composition of the Chilean population, which is an admixture of Amerindian and Spaniards, and the scarce information in the literature about similar populations.

Authors+Show Affiliations

Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17963004

Citation

De la Fuente, Marjorie K., et al. "Mutational Screening of the APC Gene in Chilean Families With Familial Adenomatous Polyposis: Nine Novel Truncating Mutations." Diseases of the Colon and Rectum, vol. 50, no. 12, 2007, pp. 2142-8.
De la Fuente MK, Alvarez KP, Letelier AJ, et al. Mutational screening of the APC gene in Chilean families with familial adenomatous polyposis: nine novel truncating mutations. Dis Colon Rectum. 2007;50(12):2142-8.
De la Fuente, M. K., Alvarez, K. P., Letelier, A. J., Bellolio, F., Acuña, M. L., León, F. S., Pinto, E., Carvallo, P., & López-Köstner, F. (2007). Mutational screening of the APC gene in Chilean families with familial adenomatous polyposis: nine novel truncating mutations. Diseases of the Colon and Rectum, 50(12), 2142-8.
De la Fuente MK, et al. Mutational Screening of the APC Gene in Chilean Families With Familial Adenomatous Polyposis: Nine Novel Truncating Mutations. Dis Colon Rectum. 2007;50(12):2142-8. PubMed PMID: 17963004.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mutational screening of the APC gene in Chilean families with familial adenomatous polyposis: nine novel truncating mutations. AU - De la Fuente,Marjorie K, AU - Alvarez,Karin P, AU - Letelier,Alejandro J, AU - Bellolio,Felipe, AU - Acuña,Mariana L, AU - León,Francisca S, AU - Pinto,Eliana, AU - Carvallo,Pilar, AU - López-Köstner,Francisco, PY - 2007/10/27/pubmed PY - 2008/2/8/medline PY - 2007/10/27/entrez SP - 2142 EP - 8 JF - Diseases of the colon and rectum JO - Dis. Colon Rectum VL - 50 IS - 12 N2 - PURPOSE: Familial adenomatous polyposis is characterized by the development of hundreds of adenomatous polyps located mainly in the colon and rectum. Patients with familial adenomatous polyposis who do not receive treatment will develop cancer before aged 40 years. This disease is caused by germline mutations in the adenomatous polyposis coli gene. Different studies have shown a correlation between the location of the mutation and the clinical phenotype, such as the grade of severity and/or the presence of extracolonic manifestations, such as desmoid tumors. This study was designed to identify germline mutation in the adenomatous polyposis coli gene in Chilean families with familial adenomatous polyposis. METHODS: We examined the adenomatous polyposis coli gene in 24 Chilean families with familial adenomatous polyposis. The adenomatous polyposis coli gene was screened for mutations combining single strand conformation polymorphism technique, protein truncation test, and DNA sequencing. RESULTS: We detected 17 different truncating mutations in 21 of 24 families (87.5 percent); 9 of these were novel. Fourteen mutations were detected in exon 15, being the most frequent c.3,927_3,931delAAAGA, found in 3 of 21 families (14 percent). Eight families (33 percent) showed at least one patient affected with desmoid tumors, presenting mutations between codons 849 and 1,533. Interestingly, two mutations, c.3,632dupA and c.3,783_3,784delTT, leading into a truncating protein at codons 1,216 and 1,274, were associated with almost 100 percent penetrance for desmoid tumors among relatives. CONCLUSIONS: We achieved 87 percent mutation detection rate in adenomatous polyposis coli gene; more than 50 percent of them were novel. The high percentage of novel mutations found may be because of the genetic composition of the Chilean population, which is an admixture of Amerindian and Spaniards, and the scarce information in the literature about similar populations. SN - 0012-3706 UR - https://www.unboundmedicine.com/medline/citation/17963004/Mutational_screening_of_the_APC_gene_in_Chilean_families_with_familial_adenomatous_polyposis:_nine_novel_truncating_mutations_ L2 - http://link.springer.com/article/10.1007/s10350-007-9044-z DB - PRIME DP - Unbound Medicine ER -