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A search for germline APC mutations in early onset colorectal cancer or familial colorectal cancer with normal DNA mismatch repair.
Genes Chromosomes Cancer. 2001 Feb; 30(2):181-6.GC

Abstract

Twenty percent of colorectal cancers (CRCs) arise in people who have a family history of CRC in at least one other relative. Although a fraction of these CRCs are explained by two well-described autosomal dominant syndromes-5% by hereditary nonpolyposis colorectal cancer (HNPCC) and 1% by familial adenomatous polyposis (FAP)-the cause of the remaining 14% of familial aggregates of CRC is unknown. Many cases of HNPCC are due to germline mutations in DNA mismatch repair genes, leading to the tumor phenotype of microsatellite instability (MSI), and most cases of FAP are caused by germline APC mutations. To date, non-FAP familial CRC aggregates have not been evaluated for germline APC mutations. In this study, we examined the involvement of germline APC mutations in 79 individuals with CRC who had early-age onset of their cancer (age < 50 years) and/or a family history of CRC. Cases with FAP or HNPCC due to defective mismatch repair were excluded from the study. Using conformation-sensitive gel electrophoresis and the protein truncation test as the screening methods, no functionally significant germline mutations were detected for any of the cases. An apparently silent polymorphism resulting in a 1-bp alteration of A --> G (proline --> proline) in exon 4 was observed. Additionally, four intervening sequence (IVS) alterations were detected: IVS2-53t-->c in 3 cases; IVS4-17ins T in 3 cases; IVS5+32t-->c in 16 cases; and IVS5+33g-->a in 1 case. All appeared to be polymorphisms present in similar proportions in an average-risk population. We conclude that germline APC mutations do not account for familial MSS (stable microsatellite) CRC associated with few synchronous polyps.

Authors+Show Affiliations

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota 55905, USA. boardman.lisa@mayo.eduNo 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, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11135435

Citation

Boardman, L A., et al. "A Search for Germline APC Mutations in Early Onset Colorectal Cancer or Familial Colorectal Cancer With Normal DNA Mismatch Repair." Genes, Chromosomes & Cancer, vol. 30, no. 2, 2001, pp. 181-6.
Boardman LA, Schmidt S, Lindor NM, et al. A search for germline APC mutations in early onset colorectal cancer or familial colorectal cancer with normal DNA mismatch repair. Genes Chromosomes Cancer. 2001;30(2):181-6.
Boardman, L. A., Schmidt, S., Lindor, N. M., Burgart, L. J., Cunningham, J. M., Price-Troska, T., Snow, K., Ahlquist, D. A., & Thibodeau, S. N. (2001). A search for germline APC mutations in early onset colorectal cancer or familial colorectal cancer with normal DNA mismatch repair. Genes, Chromosomes & Cancer, 30(2), 181-6.
Boardman LA, et al. A Search for Germline APC Mutations in Early Onset Colorectal Cancer or Familial Colorectal Cancer With Normal DNA Mismatch Repair. Genes Chromosomes Cancer. 2001;30(2):181-6. PubMed PMID: 11135435.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A search for germline APC mutations in early onset colorectal cancer or familial colorectal cancer with normal DNA mismatch repair. AU - Boardman,L A, AU - Schmidt,S, AU - Lindor,N M, AU - Burgart,L J, AU - Cunningham,J M, AU - Price-Troska,T, AU - Snow,K, AU - Ahlquist,D A, AU - Thibodeau,S N, PY - 2001/1/3/pubmed PY - 2001/3/3/medline PY - 2001/1/3/entrez SP - 181 EP - 6 JF - Genes, chromosomes & cancer JO - Genes Chromosomes Cancer VL - 30 IS - 2 N2 - Twenty percent of colorectal cancers (CRCs) arise in people who have a family history of CRC in at least one other relative. Although a fraction of these CRCs are explained by two well-described autosomal dominant syndromes-5% by hereditary nonpolyposis colorectal cancer (HNPCC) and 1% by familial adenomatous polyposis (FAP)-the cause of the remaining 14% of familial aggregates of CRC is unknown. Many cases of HNPCC are due to germline mutations in DNA mismatch repair genes, leading to the tumor phenotype of microsatellite instability (MSI), and most cases of FAP are caused by germline APC mutations. To date, non-FAP familial CRC aggregates have not been evaluated for germline APC mutations. In this study, we examined the involvement of germline APC mutations in 79 individuals with CRC who had early-age onset of their cancer (age < 50 years) and/or a family history of CRC. Cases with FAP or HNPCC due to defective mismatch repair were excluded from the study. Using conformation-sensitive gel electrophoresis and the protein truncation test as the screening methods, no functionally significant germline mutations were detected for any of the cases. An apparently silent polymorphism resulting in a 1-bp alteration of A --> G (proline --> proline) in exon 4 was observed. Additionally, four intervening sequence (IVS) alterations were detected: IVS2-53t-->c in 3 cases; IVS4-17ins T in 3 cases; IVS5+32t-->c in 16 cases; and IVS5+33g-->a in 1 case. All appeared to be polymorphisms present in similar proportions in an average-risk population. We conclude that germline APC mutations do not account for familial MSS (stable microsatellite) CRC associated with few synchronous polyps. SN - 1045-2257 UR - https://www.unboundmedicine.com/medline/citation/11135435/A_search_for_germline_APC_mutations_in_early_onset_colorectal_cancer_or_familial_colorectal_cancer_with_normal_DNA_mismatch_repair_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=1045-2257&amp;date=2001&amp;volume=30&amp;issue=2&amp;spage=181 DB - PRIME DP - Unbound Medicine ER -