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Background:Hereditary breast cancer comprises 5-10% of all breast cancers. Mutations in two high-risk susceptibility genes, BRCA1 and BRCA2, along with rare intermediate-risk genes and common low-penetrance alleles identified, altogether explain no more than 45% of the high-risk breast cancer families, although the majority of cases are unaccounted for and are designated as BRCAX tumours. Micro RNAs have called great attention for classification of different cancer types and have been implicated in a range of important biological processes and are deregulated in cancer pathogenesis.Methods:Here we have performed an exploratory hypothesis-generating study of miRNA expression profiles in a large series of 66 primary hereditary breast tumours by microarray analysis.Results:Unsupervised clustering analysis of miRNA molecular profiles revealed distinct subgroups of BRCAX tumours, 'normal-like' BRCAX-A, 'proliferative' BRCAX-B, 'BRCA1/2-like' BRCAX-C and 'undefined' BRCAX-D subgroup. These findings introduce a new insight in the biology of hereditary breast cancer, defining specific BRCAX subgroups, which could help in the search for novel susceptibility pathways in hereditary breast cancer.Conclusion:Our data demonstrate that BRCAX hereditary breast tumours can be sub-classified into four previously unknown homogenous groups characterised by specific miRNA expression signatures and histopathological features. [ABSTRACT FROM AUTHOR]

Expression profiling using DNA microarrays has been very helpful to improve our knowledge of the pathobiology of many tumour types, including lymphomas. Peripheral T-cell lymphomas (PTCL) constitute an heterogeneous group of tumours with different morphologic, immunophenotypic, and clinical characteristics. Their complexity and their low frequency in the western countries have made difficult the identification of molecular events responsible of the development of these tumours. The first studies on expression profiling of PTCL have also revealed heterogeneity at this level, mainly regarding the PTCL NOS subgroup. Different molecular subgroups within PTCL unspecified have been identified associated to different expression profiles. However, the clinical significance of this molecular sub-classification remains to be probed in studies involving larger number of samples. In addition, the expression level of NF-kB pathway genes allowed to differentiate two PTCL subgroups, and this difference could have clinical interest. In general, PTCL expression profiles are difficult to interpret due to the significant proportion of other infiltrating cells accompanying the tumour. However, microarrays are being a helpful tool in the initial task of dissecting the PTCL expression profile. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

T cell non-Hodgkin's lymphomas are a heterogeneous group of lymphomas with poor prognosis, and whose genetic alterations are not well understood. Comparative genomic hybridization (CGH) is a technique that allows the identification of DNA imbalances without cytogenetic studies. We have studied 37 samples from 29 T cell non-Hodgkin's lymphomas (25 peripheral and four lymphoblastic lymphomas) by CGH in order to detect DNA sequence copy number changes of putative importance in the biology and prognosis of these neoplasms. We detected abnormal CGH profiles in 16/27 (59%) of samples at diagnosis, a ratio that increased to 66% (23/37) when we included the relapsed samples. The most common recurrent changes were gains related to the X chromosome, either the whole chromosome or partially the Xq26-27 bands (19%). Other recurrent changes included gains of bands 9q34, gains of chromosomes 17, 19, and 20, and complete or partial deletions of chromosome 13 (10%). Cancer-related genes located at Xq26-28 region were analyzed by Southern blot and fluorescence in situ hybridization (FISH). Low level amplification of some of these genes was detected by this technique confirming the results obtained by CGH in this region. The detection of abnormal CGH profiles in these T cell lymphomas could have clinical implications. Patients with abnormal CGH profiles showed significant associations with advanced stage of disease, overexpression of P53, and higher proliferative index. [ABSTRACT FROM AUTHOR]

P15 (MTS2) gene is a candidate tumor suppressor gene localized adjacent to the p16 gene at 9p21. Deletions at the 9p21 region frequently affect both p16 and p15 genes, however, mutations in the coding sequence of the p15 gene have not been found in the majority of tumors analyzed, including non-Hodgkin's lymphomas. Abnormal methylation of the promoter region of p15 has been recently described as an alternative mechanism of inactivation of this gene. We analyzed 72 non-Hodgkin's lymphomas (NHL) for methylation at p15 exon 1 by PCR and Southern blot techniques using methylation-sensitive restriction enzymes. Abnormal methylation was found in eight cases (11%), most of them (three MALT, one anaplastic T cell lymphoma, one Burkitt and one follicular lymphoma) showing hypermethylation in the p16 gene also. In contrast, two pleomorphic T cell NHL showed a selective methylation at p15 gene, while the p16 gene remained unmethylated. The results show that methylation at the p15 gene is frequently associated with p16 methylation in NHL, and suggest that selective methylation of p15, although uncommon, could be a specific alteration implicated in T cell NHL. [ABSTRACT FROM AUTHOR]

Hypermethylation of a 5' CpG island of p16 gene has been recently described as a possible way of inactivation of this tumor suppressor gene, alternative to deletions and mutations. We have investigated if hypermethylation of a 5' CpG island of p16 occurs in non-Hodgkin's lymphoma (NHL) and normal lymphoid tissue. A total of 82 NHLs were examined for p16 methylation by Southern blot and PCR analysis. Hypermethylation was detected in approximately 20% of B cell lymphomas of both low and high grade and in 15% of T cell NHL. The highest rate of p16 gene methylation in tumors was found among MALT (mucosa-associated lymphoid tissue) lymphomas in which the percentage of cases with p16 gene methylation reached 67%. However, normal lymphoid tissue was always unmethylated at p16 locus. These results indicate that p16 gene methylation is a frequent event in NHLs, mainly in MALT lymphomas, and suggest that it could be an important mechanism of inactivation of this gene. [ABSTRACT FROM AUTHOR]