30 research outputs found
Larissa Tracy, ed. and trans., Women of the Gilte Legende: A Selection of Middle English Saint Lives. (Library of Medieval Women.) D. S. Brewer, 2003
Diane Watt, trans., The Paston Women: Selected Letters. (Library of Medieval Women.) D. S. Brewer, 2004
Diane Watt, trans., The Paston Women: Selected Letters. (Library of Medieval Women.) D. S. Brewer, 2004
The t(2;3)(q21;q27) translocation in non-Hodgkin's lymphoma displays BCL6 mutations in the 5' regulatory region and chromosomal breakpoints distant from the gene
The BCL6 gene, mapped at the chromosomal band 3q27,
encodes a POZ/Zinc finger transcription repressor
protein. It is frequently activated in Non-Hodgkin's
lymphomas (NHL) by translocations with breakpoints
clustering in the 5' major breakpoint region (MBR) as
well as by mutations in the same region. The
translocations lead to BCL6 activation by substitution
of promoters of rearranging genes derived from the
reciprocal chromosomal partners such as IG. We report
the molecular genetic analysis of a novel t(2;3)(q21;q27)
translocation subset in NHL comprising three cases
without apparent BCL6 involvement in the translocation.
Southern blot analysis of tumor DNAs utilizing BCL6
MBR probes revealed no rearrangement in two cases.
Two rearranged bands in the third case resulted from a
deletion in one allele and a mutation in the other allele.
Southern blot analysis of DNA from one of the two
tumors without BCL6 rearrangement, using a probe
derived from the recently identified alternative breakpoint region (ABR), showed a rearrangement. The ABR
is located 200-270 kb telomeric to MBR. Mutations
were identified in the previously reported hypermutable
region of BCL6 in all three tumors. In one, the mutant
allele alone was found to be expressed by RT-PCR
analysis of RNA. These results demonstrate the presence
of 3q27 translocation breakpoints at a distance from
BCL6 suggesting distant breaks that deregulate the gene
or involvement of other genes that may be subject to
rearrangement
Subtyping of renal cortical neoplasms in fine needle aspiration biopsies using a decision tree based on genomic alterations detected by fluorescence in situ hybridization
Objectives: To improve the overall accuracy of diagnosis in needle biopsies of renal masses, especially small renal masses (SRMs), using fluorescence in situ hybridization (FISH), and to develop a renal cortical neoplasm classification decision tree based on genomic alterations detected by FISH.
Patients and Methods: Ex vivo fine needle aspiration biopsies of 122 resected renal cortical neoplasms were subjected to FISH using a series of seven-probe sets to assess gain or loss of 10 chromosomes and rearrangement of the 11q13 locus. Using specimen (nephrectomy)-histology as the ‘gold standard’, a genomic aberration-based decision tree was generated to classify specimens. The diagnostic potential of the decision tree was assessed by comparing the FISH-based classification and biopsy histology with specimen histology.
Results: Of the 114 biopsies diagnostic by either method, a higher diagnostic yield was achieved by FISH (92 and 96%) than histology alone (82 and 84%) in the 65 biopsies from SRMs (<4 cm) and 49 from larger masses, respectively. An optimized decision tree was constructed based on aberrations detected in eight chromosomes, by which the maximum concordance of classification achieved by FISH was 79%, irrespective of mass size. In SRMs, the overall sensitivity of diagnosis by FISH compared with histopathology was higher for benign oncocytoma, was similar for the chromophobe renal cell carcinoma subtype, and was lower for clear-cell and papillary subtypes. The diagnostic accuracy of classification of needle biopsy specimens (from SRMs) increased from 80% obtained by histology alone to 94% when combining histology and FISH.
Conclusion: The present study suggests that a novel FISH assay developed by us has a role to play in assisting in the yield and accuracy of diagnosis of renal cortical neoplasms in needle biopsies in particular, and can help guide the clinical management of patients with SRMs that were non-diagnostic by histology
Alternative Translocation Breakpoint Cluster Region 5' to BCL-6 in B-cell Non-Hodgkin’s Lymphoma
Chromosomal translocations involving band 3q27 with various different partner chromosomes represent a recurrent cytogenetic abnormality
in B-cell non-Hodgkin’s lymphoma. In a fraction of these translocations,
the chromosomal breakpoint is located within the 5' noncoding region of
the BCL-6 proto-oncogene where the BCL-6 major breakpoint region
(MBR) maps. As a result of the translocation, BCL-6 expression is deregulated by promoter substitution. However, between 30 and 50% of lymphomas with cytogenetically detectable translocations affecting band 3q27
retain a germ-line configuration at the BCL-6 locus. To identify possible
additional breakpoint clusters within 3q27, we cloned a t(3;14)(q27;q32)
lymphoma without MBR rearrangement and found a novel breakpoint
site located between 245 and 285 kb 5' to BCL-6. Breakpoints within this
newly described region, which we called the alternative breakpoint region
(ABR), were found to be recurrent in lymphomas carrying t(3q27) chromosomal translocations but devoid of BCL-6 MBR rearrangements. Comparative analysis of multiple lymphomas carrying rearrangements within
the ABR showed that the breakpoints cluster within a 20-kb distance.
Translocations involving the ABR may juxtapose BCL-6 to distantly
acting, heterologous transcriptional regulatory elements which cause deregulation of the proto-oncogene. The identification of BCL-6 ABR provides new tools for the diagnosis of lymphomas carrying aberrations at
3q27 and deregulated BCL-6 genes
Alternative Translocation Breakpoint Cluster Region 5' to BCL-6 in B-cell Non-Hodgkin’s Lymphoma
Chromosomal translocations involving band 3q27 with various different partner chromosomes represent a recurrent cytogenetic abnormality
in B-cell non-Hodgkin’s lymphoma. In a fraction of these translocations,
the chromosomal breakpoint is located within the 5' noncoding region of
the BCL-6 proto-oncogene where the BCL-6 major breakpoint region
(MBR) maps. As a result of the translocation, BCL-6 expression is deregulated by promoter substitution. However, between 30 and 50% of lymphomas with cytogenetically detectable translocations affecting band 3q27
retain a germ-line configuration at the BCL-6 locus. To identify possible
additional breakpoint clusters within 3q27, we cloned a t(3;14)(q27;q32)
lymphoma without MBR rearrangement and found a novel breakpoint
site located between 245 and 285 kb 5' to BCL-6. Breakpoints within this
newly described region, which we called the alternative breakpoint region
(ABR), were found to be recurrent in lymphomas carrying t(3q27) chromosomal translocations but devoid of BCL-6 MBR rearrangements. Comparative analysis of multiple lymphomas carrying rearrangements within
the ABR showed that the breakpoints cluster within a 20-kb distance.
Translocations involving the ABR may juxtapose BCL-6 to distantly
acting, heterologous transcriptional regulatory elements which cause deregulation of the proto-oncogene. The identification of BCL-6 ABR provides new tools for the diagnosis of lymphomas carrying aberrations at
3q27 and deregulated BCL-6 genes
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Gene Dosage Alterations Revealed by cDNA Microarray Analysis in Cervical Cancer: Identification of Candidate Amplified and Overexpressed Genes
Cervical cancer (CC) cells exhibit complex karyotypic alterations, which is consistent with deregulation of numerous critical genes in its formation and progression. To characterize this karyotypic complexity at the molecular level, we used cDNA array comparative genomic hybridization (aCGH) to analyze 29 CC cases and identified a number of over represented and deleted genes. The aCGH analysis revealed at least 17 recurrent amplicons and six common regions of deletions. These regions contain several known tumor-associated genes, such as those involved in transcription, apoptosis, cytoskeletal remodeling, ion-transport, drug metabolism, and immune response. Using the fluorescence in situ hybridization (FISH) approach we demonstrated the presence of high-level amplifications at the 8q24.3, 11q22.2, and 20q13 regions in CC cell lines. To identify amplification-associated genes that correspond to focal amplicons, we examined one or more genes in each of the 17 amplicons by Affymetrix U133A expression arrays and semiquantitative reverse-transcription PCR (RT-PCR) in 31 CC tumors. This analysis exhibited frequent and robust upregulated expression in CC relative to normal cervix for genes EPHB2 (1p36), CDCA8 (1p34.3), AIM2 (1q22-23), RFC4, MUC4, and HRASLS (3q27-29), SKP2 (5p12-13), CENTD3 (5q31.3), PTK2, RECQL4 (8q24), MMP1 and MMP13 (11q22.2), AKT1 (14q32.3), ABCC3 (17q21-22), SMARCA4 (19p13.3) LIG1 (19q13.3), UBE2C (20q13.1), SMC1L1 (Xp11), KIF4A (Xq12), TMSNB (Xq22), and CSAG2 (Xq28). Thus, the gene dosage and expression profiles generated here have enabled the identification of focal amplicons characteristic for the CC genome and facilitated the validation of relevant genes in these amplicons. These data, thus, form an important step toward the identification of biologically relevant genes in CC pathogenesis
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Dance, Institution, Abolition
Antiracist commitments—in medieval studies and elsewhere—are incomplete without a commitment to abolitionist principles. These principles involve the dismantling of police, prisons, and many other institutions fostering the interests of carcerality, property protection, and racial capitalism. This essay encourages scholars of medieval dance to explore abolitionist horizons because, it argues, the study of medieval dance requires the development of three capacities also integral to the abolitionist project: 1) an ability to envision what we cannot know; 2) an understanding of how to act collectively even through our estrangement from each other (as medieval dancers did); 3) a willingness to take risks. These characteristics could help scholars of dance confront medieval studies and mobilize it to make not just the field but also the world a place of freedom, thriving, and mutual care