35 research outputs found
RASSF2 (Ras association (RalGDS/AF-6) domain family member 2)
No full textReview on RASSF2 (Ras association (RalGDS/AF-6) domain family member 2), with data on DNA, on the protein encoded, and where the gene is implicated
The novel <i>RASSF6</i> and <i>RASSF10</i> candidate tumour suppressor genes are frequently epigenetically inactivated in childhood leukaemias
No full textBackground: The Ras-assocation family (RASSF) of tumour suppressor genes (TSGs) contains 10 members that encode proteins containing Ras-assocation (RA) domains. Several members of the RASSF family are frequently epigenetically inactivated in cancer, however, their role in leukaemia has remained largely uninvestigated. Also, RASSF10 is a predicted gene yet to be experimentally verified. Here we cloned, characterised and demonstrated expression of RASSF10 in normal human bone marrow. We also determined the methylation status of CpG islands associated with RASSF1-10 in a series of childhood acute lymphocytic leukaemias (ALL) and normal blood and bone marrow samples. Results: COBRA and bisulphite sequencing revealed RASSF6 and RASSF10 were the only RASSF members with a high frequency of leukaemia-specific methylation. RASSF6 was methylated in 94% (48/51) B-ALL and 41% (12/29) T-ALL, whilst RASSF10 was methylated in 16% (8/51) B-ALL and 88% (23/26) T-ALL. RASSF6 and RASSF10 expression inversely correlated with methylation which was restored by treatment with 5-aza-2'deoxycytidine (5azaDC). Conclusion: This study shows the hypermethylation profile of RASSF genes in leukaemias is distinct from that of solid tumours and represents the first report of inactivation of RASSF6 or RASSF10 in cancer. These data show epigenetic inactivation of the candidate TSGs RASSF6 and RASSF10 is an extremely frequent event in the pathogenesis of childhood leukaemia. This study also warrants further investigation of the newly identified RASSF member RASSF10 and its potential role in leukaemia
Sanders - Charles F. Sanders (ca. 1892)
No full textA.B.; A.M., 1895; entered sophomore class; Phi Beta Kappa; Kappa Phi Kappa; Pi Gamma Mu. Grad. Gettysburg Seminary, 1895; D.D., Lafayette C., 1913. Born Feb. 11, 1869, Mifflinburg. Teacher, 1888-89. Lutheran clergyman: Avonmore, 1895-98; Blairsville, 1898-1905. Professor of Economics, Blairsville C. for Women, 1900-05. Student at Leipzig U., 1905-06. Professor of Philosophy, Gettysburg College, 1906- . Translator: Jerusalem's "Introduction to Philosophy", Jerusalem's "Problems of the Secondary Teacher", and Jerusalem's "Introduction to Philosophy", revised and enlarged; Hoeffding, "Brief History of Modern Philosophy". Author: "The Taproot of Religion and its Fruitage". Married Dec. 27, 1894, Harriet E. Hesson, Taneytown, Md. Address: 135 Broadway, Gettysburg
Factor structures of three measures of research self-efficacy
No full textMeasures of research self-efficacy have the potential to facilitate graduate training and mentoring, but the hypothesized factor structures of these measures have not been confirmed empirically. Moreover, the underlying dimensions of research self-efficacy across multiple measures are unknown. Graduate students in psy-ch via es io ca fo and persistence in a career field (Lent, Brown, & Hackett, 1994). Because of the ional theory, the assessment of self-efficacy t part of career assessment (Betz & Borgen, 6). in science-related fields, self-efficacy with respect to conducting research is critical. Research self-efficacy may be defined he second hological is article. sychology,This research was based on a master’s thesis conducted by the first author under the direction of
Abstract LB-375: Inactivation of the deubiquitinase USP44 is an early event in the formation of colorectal cancer
No full textReduced nuclear DNA methylation and mitochondrial transcript changes in adenomas do not associate with mtDNA methylation
No full textBackground: Altered mitochondrial function and large-scale changes to DNA methylation patterns in the nuclear genome are both hallmarks of colorectal cancer (CRC). Mitochondria have multiple copies of a 16 kb circular genome that contains genes that are vital for their function. While DNA methylation is known to alter the nuclear genome in CRC, it is not clear whether it could have a similar influence in mtDNA; indeed, currently, the issue of whether mitochondrial genome (mtDNA) methylation occurs is controversial. Thus our goal here was to determine whether the methylation state of mtDNA is linked to mitochondrial gene transcription in colorectal adenomas, and to assess its suitability as a biomarker in CRC. Methods: To investigate the relationship between DNA methylation and mitochondrial transcripts in adenomas, we performed RNA-sequencing and Whole Genome Bisulphite Sequencing (WGBS) of mtDNA-enriched DNA from normal mucosa and paired adenoma patient samples. Results: Transcriptional profiling indicated that adenomas had reduced mitochondrial proton transport versus normal mucosa, consistent with altered mitochondrial function. The expression of 3 tRNAs that are transcribed from mtDNA were also decreased in adenoma. Overall methylation of CG dinucleotides in the nuclear genome was reduced in adenomas (68%) compared to normal mucosa (75%, P < 0.01). Methylation in mtDNA was low (1%) in both normal and adenoma tissue but we observed clusters of higher methylation at the ribosomal RNA genes. Levels of methylation within these regions did not differ between normal and adenoma tissue. Conclusions: We provide evidence that low-level methylation of specific sites does exist in the mitochondrial genome but that it is not associated with mitochondrial gene transcription changes in adenomas. Furthermore, as no large scale changes to mtDNA methylation were observed it is unlikely to be a suitable biomarker for early-stage CRC.published_or_final_versio
Analysis of the Birt-Hogg-Dubé (BHD) tumour suppressor gene in sporadic renal cell carcinoma and colorectal cancer
No full textGermline mutations in the BHD gene cause the dominantly inherited cancer susceptibility disorder, Birt - Hogg - Dube ' ( BHD) syndrome. Individuals with BHD are reported to have an increased risk of renal cell carcinoma ( RCC) and of colorectal polyps and cancer. The BHD gene maps to 17p11.2, and to investigate whether somatic inactivation of the BHD gene region is implicated in the pathogenesis of sporadic RCC and colorectal cancer ( CRC), we performed mutation analysis in 30 RCC primary tumours and cell lines, and 35 CRCs and cell lines. A somatic missense mutation ( Ala444Ser) with loss of the wild type allele ( consistent with a two hit mechanism of tumorigenesis) was detected in a primary clear cell RCC, and a further missense mutation ( Ala238Val) was identified in a clear cell RCC cell line for which matched normal DNA was not available. A somatic missense substitution ( Arg392Gly) was identified in a primary CRC, and the same change was detected in three RCCs ( all oncocytomas) for which matched normal DNA was not available. A germline Arg320Gln missense variant detected in a primary CRC was not detected in 40 control individuals or in a further 159 familial and sporadic CRC cases. However, AA homozygotes for an intronic single nucleotide polymorphism ( c. 1517+ 6 G --> A) were under-represented in familial cases compared with controls ( p = 0.03). For some tumour suppressor genes, epigenetic silencing is a more common mechanism of inactivation than somatic mutations. However, we did not detect evidence of epigenetic silencing of BHD in 19 CRC and RCC cell lines, and BHD promoter region hypermethylation was not detected in 20 primary RCCs. These findings suggest that BHD inactivation occurs in a subset of clear cell RCC CRC
