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Four novel germline mutations in the MLH1 and PMS2 mismatch repair genes in patients with hereditary nonpolyposis colorectal cancer.
Int J Colorectal Dis 2009; 24(8):885-93IJ

Abstract

BACKGROUND

Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common cause of early onset hereditary colorectal cancer. In the majority of HNPCC families, microsatellite instability (MSI) and germline mutation in one of the DNA mismatch repair (MMR) genes are found.

MATERIALS AND METHODS

The entire coding sequence of MMR genes (MLH1, MLH2, MLH6, and PMS2) was analyzed using direct sequencing. Also, tumor tests were done as MSI and immunohistochemistry testing.

RESULTS

We were able to find three novel MLH1 and one novel PMS2 germline mutations in three Iranian HNPCC patients. The first was a transversion mutation c.346A>C (T116P) and happened in the highly conserved HATPase-c region of MLH1 protein. The second was a transversion mutation c.736A>T (I246L), which caused an amino acid change of isoleucine to leucine. The third mutation (c.2145,6 delTG) was frameshift and resulted in an immature stop codon in five codons downstream. All of these three mutations were detected in the MLH1 gene. The other mutation was a transition mutation, c.676G>A (G207E), which has been found in exon six of the PMS2 gene and caused an amino acid change of glycine to glutamic acid. MSI assay revealed high instability in microsatellite for two patients and microsatellite stable for one patient.

CONCLUSION

In all patients, an abnormal expression of the MMR proteins in HNPCC was related to the above novel mutations.

Authors+Show Affiliations

Research Center for Gastroenterology and Liver Diseases, Taleghani Hospital, Shaheed Beheshti Medical University, Tehran, Iran. mah_haghighi@hotmail.comNo 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

Language

eng

PubMed ID

19479271

Citation

Montazer Haghighi, Mahdi, et al. "Four Novel Germline Mutations in the MLH1 and PMS2 Mismatch Repair Genes in Patients With Hereditary Nonpolyposis Colorectal Cancer." International Journal of Colorectal Disease, vol. 24, no. 8, 2009, pp. 885-93.
Montazer Haghighi M, Radpour R, Aghajani K, et al. Four novel germline mutations in the MLH1 and PMS2 mismatch repair genes in patients with hereditary nonpolyposis colorectal cancer. Int J Colorectal Dis. 2009;24(8):885-93.
Montazer Haghighi, M., Radpour, R., Aghajani, K., Zali, N., Molaei, M., & Zali, M. R. (2009). Four novel germline mutations in the MLH1 and PMS2 mismatch repair genes in patients with hereditary nonpolyposis colorectal cancer. International Journal of Colorectal Disease, 24(8), pp. 885-93. doi:10.1007/s00384-009-0731-1.
Montazer Haghighi M, et al. Four Novel Germline Mutations in the MLH1 and PMS2 Mismatch Repair Genes in Patients With Hereditary Nonpolyposis Colorectal Cancer. Int J Colorectal Dis. 2009;24(8):885-93. PubMed PMID: 19479271.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Four novel germline mutations in the MLH1 and PMS2 mismatch repair genes in patients with hereditary nonpolyposis colorectal cancer. AU - Montazer Haghighi,Mahdi, AU - Radpour,Ramin, AU - Aghajani,Katayoun, AU - Zali,Narges, AU - Molaei,Mahsa, AU - Zali,Mohammad Reza, Y1 - 2009/05/29/ PY - 2009/05/13/accepted PY - 2009/5/30/entrez PY - 2009/5/30/pubmed PY - 2009/9/9/medline SP - 885 EP - 93 JF - International journal of colorectal disease JO - Int J Colorectal Dis VL - 24 IS - 8 N2 - BACKGROUND: Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common cause of early onset hereditary colorectal cancer. In the majority of HNPCC families, microsatellite instability (MSI) and germline mutation in one of the DNA mismatch repair (MMR) genes are found. MATERIALS AND METHODS: The entire coding sequence of MMR genes (MLH1, MLH2, MLH6, and PMS2) was analyzed using direct sequencing. Also, tumor tests were done as MSI and immunohistochemistry testing. RESULTS: We were able to find three novel MLH1 and one novel PMS2 germline mutations in three Iranian HNPCC patients. The first was a transversion mutation c.346A>C (T116P) and happened in the highly conserved HATPase-c region of MLH1 protein. The second was a transversion mutation c.736A>T (I246L), which caused an amino acid change of isoleucine to leucine. The third mutation (c.2145,6 delTG) was frameshift and resulted in an immature stop codon in five codons downstream. All of these three mutations were detected in the MLH1 gene. The other mutation was a transition mutation, c.676G>A (G207E), which has been found in exon six of the PMS2 gene and caused an amino acid change of glycine to glutamic acid. MSI assay revealed high instability in microsatellite for two patients and microsatellite stable for one patient. CONCLUSION: In all patients, an abnormal expression of the MMR proteins in HNPCC was related to the above novel mutations. SN - 1432-1262 UR - https://www.unboundmedicine.com/medline/citation/19479271/Four_novel_germline_mutations_in_the_MLH1_and_PMS2_mismatch_repair_genes_in_patients_with_hereditary_nonpolyposis_colorectal_cancer_ L2 - https://dx.doi.org/10.1007/s00384-009-0731-1 DB - PRIME DP - Unbound Medicine ER -