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Interphase FISH (IFISH) analysis is an intriguing molecular cytogenetic approach to study chromosome abnormalities in cancer. IFISH is a high sensitivity technique because of its ability to identify aberrations on a cell-to-cell level. The possibility to perform IFISH on different types of nuclei obtained both from fresh and archived samples, makes this technique an advantageous method to identify specific chromosome aberrations in cancer and correlate them to prognosis and therapy. The aim of this review is to outline the technical aspects, the sensitivity and specificity and the current strategies for employment of IFISH in tumor pathology, and to discuss the enormous range of novel applications. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

A French and an Australian study have recently identified a rare germline functional variant in the microphthalmia-associated transcription factor ( MITF) ( E318 K) that predisposes to familial and sporadic melanoma and to renal cell carcinoma ( RCC), showing a new link between two tumour types with different risk factors and between deregulated sumoylation and cancer. The aim of this study was to test the prevalence of the MITF E318 K mutation in 667 Italian melanoma patients. We observed significant associations between histological subtypes and family cancer history. Carriers exhibited a nearly threefold higher risk of developing melanoma compared with controls. Carriers were also more likely to have developed multiple primary melanomas (6.40-fold), compared with wt patients. Carriers with a personal and/or family history of pancreatic cancer and kidney cancer had a nearly 31- and eightfold higher risk of developing melanoma compared with wt patients. Our findings further support MITF as a medium-penetrance melanoma susceptibility gene, highlight a potential association with histological subtypes and suggest that MITF may predispose to pancreatic cancer. [ABSTRACT FROM AUTHOR]

AIMS: (1) To validate a quantitative real time methylation specific PCR assay (MethyLight) for the detection of O6-methylguanine-DNA methyltransferase (MGMT) gene methylation status (MS) in diffuse large B-cell lymphoma (DLBCL). (2) To determine the immunohistochemical (IHC) expression of the MGMT protein and correlate it with MS. Both IHC and MethyLight results were compared with patient’s outcome. METHODS: 71 patients with primary nodal DLBCL were studied. MGMT immunoreactivity was detected using a specific monoclonal antibody. The MS of MGMT gene was analysed in 52/71 DLBCL using MethyLight. A selected subset of 40 DLBCL was also analysed using qualitative methylation-specific PCR (MSP). Statistical analysis of overall survival (OS), lymphoma-specific survival (LSS) and progression free survival (PFS) was performed according to IHC and MS results. RESULTS: 19/71 DLBCLs (27%) were MGMT-negative at IHC; all were analysed, together with 33/52 MGMT-positive DLBCLs. MethyLight showed a better performance than MSP. There was a good correlation between the presence of MGMT expression and the unmethylated status; the absence of IHC expression was poorly correlated with the presence of methylation. Better OS, LSS and PFS was found in DLBCLs with MGMT gene methylation. DLBCLs not expressing MGMT at IHC showed a longer PFS. CONCLUSIONS: The quantitative real-time methylation-specific PCR assay for the detection of MGMT gene hypermethylation has been validated for the first time in DLBCL. Immunohistochemistry seems to represent an useful preliminary test to identify unmethylated cases; MS analysis may be performed in non-immunoreactive cases to identify truly methylated DLBCLs, which bear a better prognosis. [ABSTRACT FROM AUTHOR]

Hereditary non-polyposis colorectal cancer (HNPCC) is caused by inactivating mutations of DNA mismatch repair genes. Large genomic rearrangements in these genes have been increasingly recognized as important causes of HNPCC. Using multiplex ligation-dependent probe amplification, we identified three MSH2 deletions in Italian patients with HNPCC (proband A: exons 1–3, proband M: exon 8, and proband C: exons 1–6). Deletion breakpoint sequencing allowed us to develop rapid polymerase chain reaction-based mutation screening, which confirmed the presence of the deletions in affected and asymptomatic individuals of families A, C, and M. While the exon 8 and exon 1–3 deletions appear to be novel, the MSH2 1–6 deletion found in family C is identical to the one recently documented in two branches of another unrelated Italian family (family V+Va). Haplotype analysis showed that the kindreds C and V+Va (both from northeastern Italy, both displaying clinical features of the Muir–Torre syndrome) shared a seven-locus haplotype, indicating that the MSH2 1–6 deletion is probably a founder mutation. Families A, C, M, and V+Va all showed progressively earlier cancer-onset ages in successive generations. Analysis of 23 affected parent–child pairs in the four kindreds showed median anticipation of 12 years in offsprings’ onset of cancer (p = 0.0001). No birth cohort effect was found. This is the first significant evidence of anticipation effects in HNPCC families carrying MSH2 deletions. [ABSTRACT FROM AUTHOR]