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Clinical and molecular diagnosis of hereditary non-polyposis colorectal cancer: problems and pitfalls in an extended pedigree.
Ital J Gastroenterol Hepatol. 1999 Aug-Sep; 31(6):476-80.IJ

Abstract

Hereditary non-polyposis colorectal cancer (or Lynch syndrome) is an autosomal dominant disease in which early onset colorectal carcinomas aggregate in families together with tumours of other organs. The genetic basis of the syndrome has been clarified with the identification of mutations in several DNA mismatch repair genes (MSH2, MLH1, PMS1, PMS2 and MSH6). We describe the clinical features and molecular characterization of a large hereditary non-polyposis colorectal cancer family which has been followed for almost 10 years. The kindred showed a striking aggregation of colorectal tumours in 3 successive generations; most of these neoplasms developed before the age of 50 years and were localized in the proximal colon. Molecular tests (carried out in ten individuals) showed specific alterations at the MLH1 gene, consisting in the insertion of a T nucleotide between bases 2,269 and 2,270; the mutation caused frameshift of the open reading frame and synthesis of a polypeptide longer than normal. The only tumour that could be analysed was positive for microsatellite instability. Physicians should become more confident with hereditary tumours and their implications, which are not limited to a single individual but concern all family members at risk of cancer. This family approach is different, and requires more expertise than the traditional individual approach. Common problems encountered in Hereditary Non-polyposis Colorectal Cancer families include: A) poor collaboration of subjects at risk (a situation which may cause some conflict between the doctor's duty to inform patients about their risk of disease and the rights of patients to choose and decide about their health); B) definition of the most appropriate surveillance programme for a given family (how many investigations to propose to the patients, and how often); C) possible interaction between genes and environmental factors (for instance, a gene carrier--in this family--developed an endometrial carcinoma after standard tamoxifen adjuvant therapy for breast cancer).

Authors+Show Affiliations

Department of Internal Medicine, University of Modena, Italy. deleon@unimo.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

10575566

Citation

Ponz de Leon, M, et al. "Clinical and Molecular Diagnosis of Hereditary Non-polyposis Colorectal Cancer: Problems and Pitfalls in an Extended Pedigree." Italian Journal of Gastroenterology and Hepatology, vol. 31, no. 6, 1999, pp. 476-80.
Ponz de Leon M, Benatti P, Percesepe A, et al. Clinical and molecular diagnosis of hereditary non-polyposis colorectal cancer: problems and pitfalls in an extended pedigree. Ital J Gastroenterol Hepatol. 1999;31(6):476-80.
Ponz de Leon, M., Benatti, P., Percesepe, A., Rossi, G., Viel, A., Santarosa, M., Pedroni, M., & Roncucci, L. (1999). Clinical and molecular diagnosis of hereditary non-polyposis colorectal cancer: problems and pitfalls in an extended pedigree. Italian Journal of Gastroenterology and Hepatology, 31(6), 476-80.
Ponz de Leon M, et al. Clinical and Molecular Diagnosis of Hereditary Non-polyposis Colorectal Cancer: Problems and Pitfalls in an Extended Pedigree. Ital J Gastroenterol Hepatol. 1999 Aug-Sep;31(6):476-80. PubMed PMID: 10575566.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clinical and molecular diagnosis of hereditary non-polyposis colorectal cancer: problems and pitfalls in an extended pedigree. AU - Ponz de Leon,M, AU - Benatti,P, AU - Percesepe,A, AU - Rossi,G, AU - Viel,A, AU - Santarosa,M, AU - Pedroni,M, AU - Roncucci,L, PY - 1999/11/27/pubmed PY - 1999/11/27/medline PY - 1999/11/27/entrez SP - 476 EP - 80 JF - Italian journal of gastroenterology and hepatology JO - Ital J Gastroenterol Hepatol VL - 31 IS - 6 N2 - Hereditary non-polyposis colorectal cancer (or Lynch syndrome) is an autosomal dominant disease in which early onset colorectal carcinomas aggregate in families together with tumours of other organs. The genetic basis of the syndrome has been clarified with the identification of mutations in several DNA mismatch repair genes (MSH2, MLH1, PMS1, PMS2 and MSH6). We describe the clinical features and molecular characterization of a large hereditary non-polyposis colorectal cancer family which has been followed for almost 10 years. The kindred showed a striking aggregation of colorectal tumours in 3 successive generations; most of these neoplasms developed before the age of 50 years and were localized in the proximal colon. Molecular tests (carried out in ten individuals) showed specific alterations at the MLH1 gene, consisting in the insertion of a T nucleotide between bases 2,269 and 2,270; the mutation caused frameshift of the open reading frame and synthesis of a polypeptide longer than normal. The only tumour that could be analysed was positive for microsatellite instability. Physicians should become more confident with hereditary tumours and their implications, which are not limited to a single individual but concern all family members at risk of cancer. This family approach is different, and requires more expertise than the traditional individual approach. Common problems encountered in Hereditary Non-polyposis Colorectal Cancer families include: A) poor collaboration of subjects at risk (a situation which may cause some conflict between the doctor's duty to inform patients about their risk of disease and the rights of patients to choose and decide about their health); B) definition of the most appropriate surveillance programme for a given family (how many investigations to propose to the patients, and how often); C) possible interaction between genes and environmental factors (for instance, a gene carrier--in this family--developed an endometrial carcinoma after standard tamoxifen adjuvant therapy for breast cancer). SN - 1125-8055 UR - https://www.unboundmedicine.com/medline/citation/10575566/Clinical_and_molecular_diagnosis_of_hereditary_non_polyposis_colorectal_cancer:_problems_and_pitfalls_in_an_extended_pedigree_ L2 - http://www.diseaseinfosearch.org/result/5249 DB - PRIME DP - Unbound Medicine ER -