TITLE

Identification of mismatch repair gene mutations in young patients with colorectal cancer and in patients with multiple tumours associated with hereditary non-polyposis colorectal cancer

AUTHOR(S)
Niessen, R. C.; Berends, M. J.; Wu, Y.; Sijimons, R. H.; Hollema, H.; Ligtenberg, M. J.; de Walle, H. E. K.; de Vries, E. G. E.; Karrenbeld, A.; Buys, C. H. C. M.; van der Zee, A. G. J.; Hofstra, R. M. W.; Kleibeuker, J. H.
PUB. DATE
December 2006
SOURCE
Gut;Dec2006, Vol. 55 Issue 12, p1781
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: Patients with early-onset colorectal cancer (CRC) or those with multiple tumours associated with hereditary non-polyposis colorectal cancer (HNPCC) raise suspicion of the presence of germline DNA mismatch repair (MMR) gene mutations. Aim: To analyse the value of family history, microsatellite instability (MSI) analysis and MMR protein staining in the tumour to predict the presence of an MMR gene mutation in such patients. Methods: In 281 patients diagnosed with CRC before the age of 50 years or with CRC and at least one additional HNPCC-associated cancer, germline mutation analysis in MLH1, MSH2 and MSH6 was carried out with denaturing gradient gel electrophoresis and multiplex ligation-dependent probe amplification. MSI analysis with five consensus markers and MMR protein staining for MLH1, MSH2 and MSH6 were carried out in the tumours. Results: 25 pathogenic mutations (8 in MLH1, 9 in MSH2 and 8 in MSH6) were found. MSI analysis missed three and immunohistochemistry (IHC) missed two mutation carriers. Sensitivities of family history, MSI analysis and IHC for the presence of a mutation were 76%, 82% and 88%, specificities were 64%, 70% and 84%, and positive predictive values were 19%, 23% and 38%, respectively. Multivariate analysis showed the highest odds ratio for IHC (38.3, 95% confidence interval 9.0 to 184). Prevalence of pathogenic germline MMR gene mutations in patients with CRC before the age of 50 years was 6% and in those with ⩾2 HNPCC-associated tumours was 22%. In the second group, no mutation carriers were found among the 29 patients who were diagnosed with their first tumour after the age of 60 years. Conclusion: Family history, MSI analysis and IHC are indicative parameters to select patients with CRC for MMR gene mutation analysis. The data show that IHC is the best single selection criterion.
ACCESSION #
23512276

 

Related Articles

  • Association between family history and mismatch repair in colorectal cancer. Coggins, R. P.; Cawkwell, L.; Bell, S. M.; Crockford, G. P.; Quirke, P.; Finan, P. J.; Bishop, D. T. // Gut;May2005, Vol. 54 Issue 5, p636 

    Background and aims: Germline mutations in mismatch repair (MMR) genes cause a greatly increased risk of cancer of the gastrointestinal and female reproductive tracts (hereditary non-polyposis colorectal cancer (HNPCC)). Loss of MMR expression is common in colorectal cancer (CRC) overall. Such...

  • P53 abnormalities and outcomes in colorectal cancer: a systematic review. Munro, A. J.; Lain, S.; Lane, D. P. // British Journal of Cancer;2/14/2005, Vol. 92 Issue 3, p434 

    We performed a systematic review of studies that investigated the effect of abnormalities of the tumour suppressor gene p53 upon prognosis in patients with colorectal cancer. The methods used to assess p53 status were immunohistochemistry (IHC), indicating abnormal accumulation of p53, and...

  • ALK gene amplification is associated with poor prognosis in colorectal carcinoma. Bavi, P; Jehan, Z; Bu, R; Prabhakaran, S; Al-Sanea, N; Al-Dayel, F; Al-Assiri, M; Al-Halouly, T; Sairafi, R; Uddin, S; Al-Kuraya, K S // British Journal of Cancer;11/12/2013, Vol. 109 Issue 10, p2735 

    Background:Recently, the anaplastic lymphoma kinase (ALK) has been found to be altered in several solid and haematological tumours. ALK gene copy number changes and mutations in colorectal cancers (CRCs) are not well characterised. We aimed to study the prevalence of ALK copy number changes,...

  • KRAS and BRAF Mutation Detection: Is Immunohistochemistry a Possible Alternative to Molecular Biology in Colorectal Cancer? Piton, Nicolas; Borrini, Francesco; Bolognese, Antonio; Lamy, Aude; Sabourin, Jean-Christophe // Gastroenterology Research & Practice;4/23/2015, Vol. 2015, p1 

    KRAS genotyping is mandatory in metastatic colorectal cancer treatment prior to undertaking antiepidermal growth factor receptor (EGFR) monoclonal antibody therapy. BRAF V600E mutation is often present in colorectal carcinoma with CpG island methylator phenotype and microsatellite instability....

  • Synchronous lung tumours in a patient with metachronous colorectal carcinoma and a germline MSH2 mutation. A Canney // Journal of Clinical Pathology;May2009, Vol. 62 Issue 5, p471 

    Mutations of DNA mismatch repair genes are characterised by microsatellite instability and are implicated in carcinogenesis. This mutation susceptible phenotype has been extensively studied in patients with hereditary non-polyposis colon carcinoma, but little is known of the contribution of such...

  • EGFR gene copy number assessment from areas with highest EGFR expression predicts response to anti-EGFR therapy in colorectal cancer. Ålgars, A.; Lintunen, M.; Carpén, O.; Ristamäki, R.; Sundström, J. // British Journal of Cancer;7/4/2011, Vol. 105 Issue 2, p255 

    Background:Only 40-70% of metastatic colorectal cancers (mCRCs) with wild-type (WT) KRAS oncogene respond to anti-epidermal growth factor receptor (anti-EGFR) antibody treatment. EGFR amplification has been suggested as an additional marker to predict the response. However, improved methods for...

  • Colorectal cancer in Iran: immunohistochemical profiles of four mismatch repair proteins. Molaei, Mahsa; Mansoori, Babak Khoshkrood; Ghiasi, Somayeh; Khatami, Fatemeh; Attarian, Hamid; Zali, MohammadReza // International Journal of Colorectal Disease;Jan2010, Vol. 25 Issue 1, p63 

    The aim of the present study was to determine the profile of mismatch repair (MMR) defects in Iranian colorectal cancer patients by using immunohistochemical staining for products of four MMR genes: MLH1, MSH2, PMS2, and MSH6. Tissue samples of 343 patients were immunostained for MLH1, MSH2,...

  • PIK3CA Activating Mutation in Colorectal Carcinoma: Associations with Molecular Features and Survival. Rosty, Christophe; Young, Joanne P.; Walsh, Michael D.; Clendenning, Mark; Sanderson, Kristy; Walters, Rhiannon J.; Parry, Susan; Jenkins, Mark A.; Win, Aung Ko; Southey, Melissa C.; Hopper, John L.; Giles, Graham G.; Williamson, Elizabeth J.; English, Dallas R.; Buchanan, Daniel D. // PLoS ONE;Jun2013, Vol. 8 Issue 6, p1 

    Mutations in PIK3CA are present in 10 to 15% of colorectal carcinomas. We aimed to examine how PIK3CA mutations relate to other molecular alterations in colorectal carcinoma, to pathologic phenotype and survival. PIK3CA mutation testing was carried out using direct sequencing on 757 incident...

  • Detection of hMSH2 and hMLH1 mutations in Chinese hereditary non-polyposis colorectal cancer kindreds. Chang-Hua Zhang; Yu-Long He; Fang-Jin Wang; Wu Song; Xi-Yu Yuan; Dong-Jie Yang; Chuang-Qi Chen; Shi-Rong Cai; Wen-Hua Zhan // World Journal of Gastroenterology;1/14/2008, Vol. 14 Issue 2, p298 

    AIM: To establish and validate the mutation testing for identification and characterization of hereditary non-polyposis colorectal cancer (HNPCC) in suspected Chinese patients. METHODS: Five independent Chinese kindreds with HNPCC fulfilling the classical Amsterdam criteria were collected....

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sign out of this library

Other Topics