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Specific Genetic Alterations (specific + genetic_alteration)
Selected AbstractsThe role of genetic testing in soft tissue sarcomaHISTOPATHOLOGY, Issue 1 2006C R Antonescu Soft tissue tumours represent a heterogeneous group of mesenchymal lesions and their classification continues to evolve as a result of incorporating advances in cytogenetic and molecular techniques. In the last decade traditional diagnostic approaches were supplemented with a significant number of reliable molecular diagnostic tools, detecting tumour type-specific genetic alterations. In addition, the successful application of some of these techniques to formalin-fixed paraffin-embedded tissue made it possible to subject a broader range of clinical material to molecular analysis. Thus, molecular genetics has already become an integral part of the work-up in some tumours, such as paediatric small blue round cell tumours, which demonstrate characteristic translocations. Several lines of evidence suggest that sarcomas can be divided into two major genetic groups: (i) sarcomas with specific genetic alterations and usually simple karyotypes, such as reciprocal chromosomal translocations (e.g. FUS-DDIT3 in myxoid liposarcoma) and specific oncogenic mutations (e.g. KIT mutation in gastrointestinal stromal tumours); and (i) sarcomas with non-specific genetic alterations and complex unbalanced karyotypes. Some of these genetic abnormalities, including chromosomal numerical changes, translocations, gene amplifications or large deletions can be apparent at the cytogenetic level (karyotyping, fluoresence in situ hybridization), while others, such as small deletions, insertions or point mutations, require molecular genetic techniques (polymerase chain reaction and sequence analysis). This review focuses on the applicability of genetic testing in the diagnosis and prognosis of soft tissue sarcomas, and gives a realistic appraisal of the ancillary role of molecular techniques, including its advantages and limitations. [source] Mismatch repair expression in testicular cancer predicts recurrence and survivalINTERNATIONAL JOURNAL OF CANCER, Issue 8 2008Alfredo Velasco Abstract We investigated mismatch repair (MMR) gene expression in testicular cancer as a molecular marker for clinical outcome (recurrence, response to chemotherapy and death) using protein expression and specific genetic alterations associated with the presence or absence of MMR activity. One hundred sixty-two cases of paraffin-embedded testis cancer specimens were subjected to immunohistochemical analysis using monoclonal antibody for MLH1 and MSH2 MMR proteins and genetic analysis using specific polymorphic markers. The degree of MMR immunoreactivity and genetic instability in the form of loss of heterozygosity (LOH) and/or microsatellite instability (MSI) were determined by comparing matched normal and tumor tissue. The degree of immunohistochemical staining for MMR expression was associated with a shorter time to tumor recurrence, resistance to chemotherapy and death. Furthermore, clinical relapse and cancer specific death was also associated with tumors exhibiting a high degree of MSI, p = 0.01 and 0.04, respectively. In contrast, LOH was not associated with recurrence, resistance to chemotherapy or death. Therefore, MMR expression defines testis cancers with distinct molecular properties and clinical behavior, such that tumors with decreased MMR immunostaining and/or increased frequency of MSI have a shorter time to recurrence and death despite chemotherapy. © 2007 Wiley-Liss, Inc. [source] Grading gastrointestinal dysplasia and what to call it when you don't know what it is,THE JOURNAL OF PATHOLOGY, Issue 2 2007GJ Offerhaus Abstract Dysplasia in the gastrointestinal tract is defined as intraepithelial neoplasia (IEN) according to the WHO nomenclature. Neoplastic growth in the gastrointestinal tract evolves through stepwise tumour progression in which consecutive morphological stages are characterized by increasing genetic instability accompanied by specific genetic alterations. Invasive cancer is preceded by non-invasive precursor stages and the clonal epithelial cell proliferation in these pre-invasive stages is diagnosed as dysplasia or IEN. Dysplasia is therefore a marker for cancer risk and guides surveillance. Dysplasia is conventionally graded using a two-tier system and low- and high-grade dysplasia convey different connotations regarding cancer risk. This perspective argues that the critical differential diagnosis is the one between neoplastic and non-neoplastic epithelial cell proliferations and the relevance of grading dysplasia is questionable. It is furthermore expected that a molecular signature will predict the propensity to invasive carcinoma more accurately than routine histopathology in the near future. Research in this field needs to focus on a combination of biomarkers representing genetic instability, clonal mutations, and genetic clonal divergence. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Early-onset gastric carcinomas display molecular characteristics distinct from gastric carcinomas occurring at a later ageTHE JOURNAL OF PATHOLOGY, Issue 1 2004Ralph Carvalho Abstract Gastric cancer is thought to result from a combination of environmental factors and accumulation of specific genetic alterations, and consequently mainly affects older patients (>50 years of age). Fewer than 10% of patients present with the disease before 45 years of age and these young patients are thought to develop carcinomas with a different molecular genetic profile from that of sporadic carcinomas occurring at a later age. Forty early-onset gastric carcinoma resection specimens were characterized for microsatellite instability (MSI) and loss of heterozygosity status using 22 polymorphic microsatellite markers. Twenty-four biopsies were additionally evaluated for the presence of MSI. No MSI was observed in any of the cases analysed. Losses were infrequent, but were most common for the D1S234 (26.1%) and D1S1676 (17.4%) markers, flanking the RUNX3 gene; for the p53ALU (23.1%) and TP53 (15.4%) markers, near the TP53 gene; and for the D16S2624 (17.2%) marker, near the E-cadherin (CDH1) gene. All cases with loss of CDH1, as well as 6/7 cases with loss of TP53, displayed aberrant staining of the corresponding proteins, pointing to a functional role for these proteins in early-onset gastric carcinogenesis. No germline CDH1, TP53 or RUNX3 mutations were detected in any of the cases analysed. No correlation was observed between non-functional E-cadherin and the histological type of the tumours analysed. Finally, Epstein,Barr virus was not detected in any of the cases analysed. On the basis of these results, early-onset gastric carcinomas appear to have characteristics distinct from gastric carcinomas occurring at a later age. Copyright © 2004 Pathological Society of Great Britain and Ireland. 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