Germline MSH2 and MLH1 mutational spectrum in HNPCC families from Poland and the Baltic States

Hereditary Cancer Centre, Department of Genetics and Pathology, Pomeranian Academy of Medicine, Szczecin, Poland.
Journal of Medical Genetics (Impact Factor: 6.34). 11/2002; 39(10).
Source: PubMed Central
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Available from: Peter Goretzki,
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    • "DNA tests aiming to detect all known founder mutations within a population are highly valuable due to an unusually high economical effectiveness. genes such as BRCA1, MLH1, MSH2 and VHL have been studied intensively and it is known which mutations should be studied first prior to more expensive and extensive screens [36-38] in many populations. "
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    ABSTRACT: During the past decade many new molecular methods for DNA and RNA analysis have emerged. The most popular thus far have been SSCP, HET, CMC, DGGE, RFLP or ASA, which have now been replaced by methods that are more cost effective and less time consuming. Real-time amplification techniques and particularly those with the capacity of multiplexing have become commonly used in laboratory practice. Novel screening methods enable the very rapid examination of large patients series. Use of liquid handling robotics applied to the isolation of DNA or RNA, the normalisation of sample concentration, and standardization of target amplification by PCR have also contributed to a reduced risk of sample contamination and have resulted in laboratory analysis being easier and faster. The aim of this study is the introduction of a few modern techniques, most commonly used in detection of genetic predisposition to cancer.
    Hereditary Cancer in Clinical Practice 12/2012; 10(1):17. DOI:10.1186/1897-4287-10-17 · 1.47 Impact Factor
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    • "For research purposes the patient was enrolled in a LS screening project and found to be a carrier of c.2388delT mutation in the 14 exon of MSH2 gene by direct sequencing. This genetic data was included in a collaborative study report of LS mutation spectrum from the Baltic countries and Poland [9], recently referenced in InSiGHT, although this mutation and phenotype were not characterized in more detail at the time. "
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    ABSTRACT: Lynch syndrome (LS) individuals are predisposed to a variety of cancers, most commonly colorectal, uterine, urinary tract, ovarian, small bowel, stomach and biliary tract cancers. The risk of extracolonic manifestations appears to be highest in MSH2 mutations carriers. We present a carrier case with a novel MSH2 gene mutation that clearly demonstrates the broad extent of LS phenotypic expression and highlights several important clinical aspects. Current evidence suggests that colorectal tumors from LS patients tend to have better prognoses than their sporadic counterparts, however survival benefits for other cancers encountered in LS are unclear. In this article we describe a family with a novel protein truncating mutation of c.2388delT in the MSH2 gene, particularly focusing on one individual carrier affected with multiple primary cancers who is surviving 25 years on. Our report of multiple primary tumors occurring in the 12-25 years interval might suggest these patients do not succumb to other extracolonic cancers, provided they are regularly followed-up.
    Hereditary Cancer in Clinical Practice 01/2012; 10(1):1. DOI:10.1186/1897-4287-10-1 · 1.47 Impact Factor
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    • "To develop efficient DNA testing, it is important to describe the nature and frequency of mutations that are characteristic of particular ethnic groups. The MSH2 and MLH1 mutation spectrum has been investigated in the Eastern Europe region by the author in a paper from 2002 [46]*. We screened 101 HNPCC kindreds fulfilling the Amsterdam II diagnostic criteria or our suspected HNPCC criteria (Table 3). "
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    ABSTRACT: This manuscript is composed of five parts which summarize five publications in succession. Essentially, they are concerned with molecular diagnostics of Lynch syndrome and are based on studies in 238 families. The finding that young age at diagnosis is the key feature in patients with MSH2 and MLH1 mutations (Part 1) has helped to define simple criteria for the preliminary diagnosis of this syndrome. A cheaper method for the detection of mutations has been developed (Part 2) and applied to study the types of mutations and their prevalence in Poland (Part 3) and the Baltic States (Part 4). A specific feature of these mutations, i.e. presence of recurrent mutations in the majority of affected families with mutations, has suggested the feasibility of effective diagnostics with a single test disclosing all of them. An attempt to reveal other causes of familial aggregation of colorectal cancer has ruled out any association with C insertion in the NOD2 gene (Part 5).
    Hereditary Cancer in Clinical Practice 12/2006; 4(4):197-205. DOI:10.1186/1897-4287-4-4-197 · 1.47 Impact Factor
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