1,721,009 research outputs found
Methylation profiles of exocrine and neuroendocrine colorectal carcinomas using methylation-specific multiple ligation-dependent probe amplification.
Full text linkIn this study, we employed Methylation-Specific Multiple Ligation-dependent Probe Amplification (MS-MLPA) to evaluate the methylation status of 34 genes in a series 104 formalin-fixed and paraffin-embedded specimens, including 83 exocrine adenocarcinomas (CRCs) and 21 neuroendocrine cancers (NECs), previously examined for clinico-pathological and molecular features, as well as in 25 colorectal mucosae from 13 CRC patients and from12 non-neoplastic patients.
We found higher levels of promoter methylation in normal colonic tissue of CRC-patients with respect to the control group. The CpG Island Methylation Phenotype (CIMP) was observed with similar frequency in exocrine CRCs and in NECs, but different methylation profiles were present in the two tumour types. Microsatellite instability was the marker most strongly associated with CIMP. In both CRCs and NECs, CIMP+/MSI+ tumours represented a homogeneous clinicopathological entity, associated with a very good prognosis compared with the other three classes of cancers.
Our results demonstrated that MS-MLPA is a rapid and sensitive method to analyse the methylation status of multiple genes simultaneously and presents innovative aspects that may have important scientific and clinical implications. The use of DNA methylation alterations as a molecular marker system could potentially be a powerful approach to population-based screening for the early detection and for risk assessment of colorectal cancer
Identificazione del primo caso italiano di duplicazione germinale dell’esone 13 del gene BRCA1
No full textANALISI INTEGRATA DI PARAMETRI CLINICO-PATOLOGICI E MOLECOLARI NEL CARCINOMA COLORETTALE (CRC)
No full textCalretinin expression in different molecular subtypes of ER and PR negative breast carcinomas
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Identification of prognostically relevant subsets of colorectal carcinomas based on clustering analysis of pathologic and molecular data
No full textDisruption of the APC gene by t(5;7) translocation in a Turcot family
No full textTurcot syndrome (TS) refers to the combination of colorectal polyps and primary tumours of the central nervous system. TS is a heterogeneous genetic condition due to APC and/or mismatch repair germline mutations. When APC is involved the vast majority of mutations are truncating, but in approximately 20%-30% of patients with familial polyposis no germline mutation can be found. A 30-year-old Caucasian woman with a positive pedigree for TS was referred to our Genetic Counselling Service. She was negative for APC and MUTYH but showed a reciprocal balanced translocation t(5;7)(q22;p15) at chromosome analysis. FISH analysis using specific BAC probes demonstrated that 5q22 breakpoint disrupted the APC gene. Transcript analysis by MLPA and digital PCR revealed that the cytogenetic rearrangement involving the 3' end of the APC gene caused a defective expression of a truncated transcript. This result allowed cytogenetic analysis to be offered to all the other family members and segregation analysis clearly demonstrated that all the carriers were affected, whereas non-carriers did not have the polyposis. A cytogenetic approach permitted the identification of the mutation-causing disease in this family, and the segregation analysis together with the transcript study supported the pathogenetic role of this mutation. Karyotype analysis was used as a predictive test in all members of this family. This family suggests that clinically positive TS and FAP cases, which test negative with standard molecular analysis, could be easily and cost-effectively resolved by a classical and molecular cytogenetic approach
Identification of the first case of germline duplication of BRCA1 exon 13 in an Italian family
No full textIn this work we report for the first time a family in Italy with the BRCA1 ins6kbEx13 mutation, a recurrent founder mutation originating from northern Britain. After the initial identification of exon 13 duplication by multiplex ligation-dependent probe amplification (MLPA assay), we confirmed the identity of the alteration with the previously published BRCA1 ins6kbEx13 mutation, by mutation specific PCR and RT-PCR assays and by haplotype analysis. As rarely reported previously, the MLPA assay was also used to examine DNA from formalin fixed paraffin embedded (FFPE) normal tissues of other affected subjects in the family and it was the only effective method to perform a complete segregation analysis of the BRCA1 ins6kbEx13 mutation in the family. A combination of different approaches including MLPA analysis, haplotype analysis and LOH study on tumor samples of all the affected members allowed to reassess the maternal transmission of the mutation expected by the pedigree analysis. Moreover, detailed morphological analysis of breast cancers of BRCA1 ins6kbEx13 mutation carriers demonstrated a rare histological variant of breast carcinomas that has never been described in patients carrying BRCA1 mutations. Our study confirms the MLPA technique as a reliable and effective method for a primary screening for BRCA1 rearrangements also by using FFPE tissues and strongly suggests that histo-pathological, immunonohistochemical and molecular information from FFPE tumor tissues should be more often considered and integrated into routine diagnostic practice of hereditary tumors
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