Comparative genomic hybridization of germ cell tumors of the adult testis: Confirmation of karyotypic findings and identification of a 12p- amplicon

Comparative genomic hybridization (CGH) was carried out on 15 primary testicular germ cell tumors (TGCT) of adolescents and adults and two metastatic residual tumors after chemotherapeutic treatment. The results were compared with karyotypic data obtained form the same tumor specimens after direct harvesting of metaphases or short-term in vitro culture. Both techniques revealed that the most consistent abnormality in primary TGCT is gain of 12p-sequences. Although in most cases over-representation of the complete short arm was observed, CGH revealed a specific amplification of 12p11.1-p12.1 region in two independent primary tumors. In addition, loss of (parts of) chromosome 13 (always involving q31-qter), and gain of (parts of) chromosome 7 (mostly involving q11), (parts of) chromosome 8, and the X chromosome were detected in more than 25% of the tumors by this latter technique. Loss of 6q15-q21 in both re

Fluorescence in situ hybridization analysis shows the frequent occurrence of 14q32.3 rearrangements with involvement of immunoglobulin switch regions in myeloma cell lines

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Detection of cryptic subtelomeric imbalances in fetuses with ultrasound abnormalities.

Contains fulltext : 69804.pdf (publisher's version ) (Closed access)It is known from postnatal diagnosis that imbalances of the subtelomeric regions contribute significantly to idiopathic mental retardation. Consequently, subtelomere screening has been incorporated into the recommendations for the evaluation of individuals with unexplained mental retardation and a normal karyotype. Previous studies suggested that for fetuses with ultrasound abnormalities and a normal karyotype, additional screening for submicroscopic imbalances can be relevant for diagnosis and prognosis. In the present paper, we report the detection of such (subtelomeric) imbalances in three fetuses. Prenatally, the three fetuses presented with ultrasound abnormalities highly suspected of a chromosomal aberration. In two of the fetuses, routine karyotyping showed no aberrations but with MLPA or FISH a small subtelomeric imbalance, that could explain the anomalies, was detected. In the third fetus, a chromosomal abnormality was detected with routine cytogenetic analysis (del(X)(p22.1)), but this abnormality could not explain the ultrasound observations and only with subtelomere screening by MLPA a causative chromosomal aberration was detected. As the three fetuses were already prenatally suspected of a chromosomal aberration, this underlines the potential relevance of subtelomere screening in such fetuses, leading to better clinical diagnosis, prognosis and care. Furthermore, when using MLPA, the analysis can be extended to other regions of known clinical importance

High detection rate of clinically relevant genomic abnormalities in plasma cells enriched from patients with multiple myeloma

Multiple myeloma is a heterogeneous disease, which is characterized by the occurrence of specific genomic abnormalities that are both of diagnostic and prognostic relevance. Since the detection of these abnormalities through molecular-genetic techniques is hampered by the overall low percentage of plasma cells present in primary bone marrow aspirates, we assessed the efficacy of these techniques in enriched plasma cell fractions from 61 multiple myeloma patients. Using interphase FISH, genomic abnormalities could be detected in 96% of the enriched samples as compared to 61% in the cultured whole bone marrow samples. We also found that microarray-based genomic profiling of enriched plasma samples facilitates the detection of additional, possibly clinically relevant, genomic abnormalities. We conclude that the genomic delineation of enriched plasma cells from multiple myeloma patients results in a significantly increased detection rate of clinically relevant genomic abnormalities. In order to facilitate molecular-genetic data interpretation, we recommend morphological assessment of plasma cell purity after enrichment. (c) 2012 Wiley Periodicals, Inc

Identification of chromosomal abnormalities relevant to prognosis in chronic lymphocytic leukemia using multiplex ligation-dependent probe amplification.

Contains fulltext : 80406.pdf (publisher's version ) (Closed access)B-cell chronic lymphocytic leukemia (CLL) is characterized by a highly variable clinical course. Characteristic genomic abnormalities provide clinically important prognostic information. Because karyotyping and fluorescence in situ hybridization (FISH) are laborious techniques, we investigated the diagnostic efficacy of the more recently developed multiplex ligation-dependent probe amplification (MLPA) technique. MLPA and interphase FISH data of 88 CLL patients were compared for loci encompassing the 13q14 region, chromosome 12, and the ATM (11q22) and TP53 (17p13) genes. We found a perfect correlation, provided that the abnormal clone was present in at least 10-20% of the cells. Because multiple loci and multiple probes per locus were included in the MLPA assay, additional abnormalities not covered by the FISH probes were detected. Furthermore, in 13 cases deletions partly covering the 13q14.3 locus were observed, including three deletions that remained undetected by FISH. All the deletions included the noncoding RNA locus DLEU1 (previously BCMS), which is considered to be the most likely CLL-associated candidate tumor suppressor gene within the 13q14 region. We conclude that MLPA serves as a comprehensive and reliable technique for the simultaneous identification of different clinically relevant and region-specific genomic aberrations in CLL