Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neoplastic cells of Hodgkin lymphoma (HL) originating from germinal or postgerminal center B cells lose their capacity to transcribe and to express surface immunoglobulins (Ig). This defect correlates with the absence of expression of B-cell-specific transcription regulators, including PU.1, BOB1, and OCT2. These findings suggest that Ig impairment in HL is caused by the defective transcription machinery. The mechanism or mechanisms underlying failure of Hodgkin cells to express PU.1, BOB1, and OCT2 remain unclear. The genes encoding for these three respective transcription factors have been mapped at 11p11.2 (SPI1), 11q23.1 (POU2AF1), and 19q13.2 (POU2F2); these are chromosomes recurrently affected in HL. To check the genomic status of PU.1, BOB1, and OCT2 in HL, we performed metaphase fluorescence in situ hybridization (FISH) analysis of 10 HL cases using locus-specific bacterial artificial chromosome clones. FISH signal pattern was correlated with the ploidy level of each analyzed cell and showed recurrent imbalances of the studied loci. The underrepresentation of one or two analyzed regions was detected in five cases; the remaining five cases showed either random losses, a ploidy-equivalent FISH pattern, or overrepresented signals. Neither a constant loss nor genomic aberration of at least one of these genes could be observed in studied cases. These findings indicate that genomic imbalances or rearrangements are not a cause of PU.1, BOB1, and OCT2 deficiency in cHL and argue for another mechanism underlying this phenomenon.
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PMID:Alterations of loci encoding PU.1, BOB1, and OCT2 transcription regulators do not correlate with their suppressed expression in Hodgkin lymphoma. 1579 64

Follicular lymphoma (FL) constitutes the second most common non-Hodgkin lymphoma in the western world. FL carries characteristic recurrent structural genomic aberrations. However, information regarding the coding genome in FL is still evolving. Here, we describe the results of massively parallel exome sequencing and single nucleotide polymorphism 6.0 array genomic profiling of 11 highly purified FL cases, and 1 transformed FL case and the validation of selected mutations in 102 FL cases. We report the identification of 15 novel recurrently mutated genes in FL. These include frequent mutations in the linker histone genes HIST1H1 B-E (27%) and mutations in OCT2 (also known as POU2F2; 8%), IRF8 (6%), and ARID1A (11%). A subset of the mutations in HIST1H1 B-E affected binding to DNMT3B, and mutations in HIST1H1 B-E and in EZH2 or ARID1A were largely mutually exclusive, implicating HIST1H1 B-E in epigenetic deregulation in FL. Mutations in OCT2 (POU2F2) affected its transcriptional and functional properties as measured through luciferase assays, the biological analysis of stably transduced cell lines, and global expression profiling. Finally, multiple novel mutated genes located within regions of acquired uniparental disomy in FL are identified. In aggregate, these data substantially broaden our understanding of the genomic pathogenesis of FL.
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PMID:Mutations in linker histone genes HIST1H1 B, C, D, and E; OCT2 (POU2F2); IRF8; and ARID1A underlying the pathogenesis of follicular lymphoma. 2443 47