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Multiple myeloma is a clonal malignancy of plasma cells in the bone marrow. Risk stratification is partly based on cytogenetic findings that include abnormalities of the IGH locus as determined by fluorescence in situ hybridization (FISH), such as rearrangements that result in either standard-risk or high-risk gene fusions. IGH deletions have been evaluated as a group in multiple myeloma patients with respect to cumulative outcomes but have provided limited guidance. Whether these deletions have the potential to result in gene fusions and thus further stratify patients is unknown. We identified 229 IGH deletions in patients referred for plasma cell dyscrasia genetic testing over 5.5 years. Follow-up was conducted on 208 of the deletions with dual fusion FISH probes for standard-risk (IGH-CCND1) and high-risk IGH gene fusions (IGH-FGFR3, IGH-MAF, IGH-MAFB). Of all deletions identified with follow-up, 44 (21%) resulted in a gene fusion as detected by FISH, 15 (7%) of which were fusion partners associated with high-risk multiple myeloma. All fusion-positive 3'-IGH deletions (6 fusions) resulted in high-risk IGH-FGFR3 fusions. Of the 15 high-risk fusion-positive cases, eight were without other high-risk cytogenetic findings. This study is the first to evaluate the presence of IGH gene fusions upon identification of IGH deletions and to characterize the deletion locus. Importantly, these findings indicate that follow-up FISH studies with dual fusion probes should be standard of care when IGH deletions are identified in multiple myeloma., (© 2020 Wiley Periodicals, Inc.)

The t(14;18) chromosomal translocation is the most common cytogenetic abnormality in non-Hodgkin lymphoma (NHL), occurring in 70-90% of follicular lymphomas (FL) and 30-50% of diffuse large B-cell lymphomas (DLBCL). Previous t(14;18)-NHL studies have not evaluated risk factors for NHL defined by both t(14;18) status and histology. In this population-based case-control study, t(14;18) status was determined in DLBCL cases using fluorescence in situ hybridization on paraffin-embedded tumor sections. Polytomous logistic regression was used to evaluate the association between a wide variety of exposures and t(14;18)-positive (N=109) and -negative DLBCL (N=125) and FL (N=318), adjusting for sex, age, race, and study center. Taller height, more lifetime surgeries, and PCB180 exposure were associated with t(14;18)-positivity. Taller individuals (third tertile vs. first tertile) had elevated risks of t(14;18)-positive DLBCL (odds ratio [OR] = 1.8, 95% confidence interval [CI] 1.1-3.0) and FL (OR=1.4, 95%CI 1.0-1.9) but not t(14;18)-negative DLBCL. Similar patterns were seen for individuals with more lifetime surgeries (13+ vs. 0-12 surgeries; t(14;18)-positive DLBCL OR=1.4, 95%CI 0.7-2.7; FL OR=1.6, 95%CI 1.1-2.5) and individuals exposed to PCB180 greater than 20.8 ng/g (t(14;18)-positive DLBCL OR=1.3, 95%CI 0.6-2.9; FL OR=1.7, 95%CI 1.0-2.8). In contrast, termite treatment and high alpha-chlordane levels were associated with t(14;18)-negative DLBCL only, suggesting that these exposures do not act through t(14;18). Our findings suggest that putative associations between NHL and height, surgeries, and PCB180 may be t(14;18)-mediated and provide support for case-subtyping based on molecular and histologic subtypes. Future efforts should focus on pooling data to confirm and extend previous research on risk factors for t(14;18)-NHL subtypes., (Copyright © 2010 UICC.)

Polymorphism of heterochromatic regions of chromosomes 1, 9 and 16 was studied in 60 oral cancer patients, in 40 patients with oral submucous fibrosis (OSMF) and in 60 normal healthy subjects. The size heteromorphism was significantly greater (p less than 0.001) in chromosome I of the patients. Localization variants were also significantly more frequent among the patients (p less than 0.05 for OSMF and less than 0.001 for oral cancer patients). The C-band heteromorphism patterns remained comparable in OSMF and in oral cancer patients, with chromosome I being the most frequently involved. On correlating the tobacco/areca-nut chewing habit with the presence of C-band heteromorphism, we observed that C-band heteromorphism was present in 89% of the habit-free oral cancer patients and 80% of the OSMF patients with relatively shorter exposure to this habit, i.e. less than 5 years. This signifies that genetic factors are important in the causation of oral precancerous and cancerous conditions and that polymorphism of the heterochromatic regions does appear to play a role in these conditions.