Multiple myeloma as a mandibular primary - Dilemma in diagnosing rare tumours of the mandible.

Multiple myeloma (MM) is a plasma cell malignancy, and its typical radiographic presentation includes punched-out radiolucency of the skull. It is a bourgeois description of myeloma and often holds good in most cases. However, the diagnosis can get tricky when a patient walks into the clinic with non-specific signs and symptoms. Many suspicions arise when we examine a well-defined mandibular swelling, but the real picture is revealed with thorough screening. This article presents a rare mandibular swelling diagnosed as MM, emphasizing important differential diagnoses for maxillofacial surgeons and pathologists.

Evaluation of the cytogenetic profile in patients with acute leukaemia.

Acute leukaemia (AL) is a heterogeneous neoplastic disease that occurs by the growth of abnormal lymphoid and myeloid cells in the bone marrow and blood leading to acute myeloid leukaemia (AML) and acute lymphocytic leukaemia (ALL). Conventional cytogenetics is a characteristic technique to hunch chromosomal abnormalities, it helps in the diagnosis and therapeutic approach of the disease by the molecular cytogenetics technique of fluorescence in situ hybridization (FISH). Chromosomal abnormalities in AL are performed by karyotyping to confirm specific chromosomal abnormalities using FISH. The descriptive study included 42 clinically diagnosed AL patients. Karyotyping analysis was performed using the standard Giemsa banding procedure. To confirm specific chromosomal abnormalities and all culture failure (CF) cases, FISH was done. Among 42 cases, 29 (69.4%) males and 13 (30.9%) females, AML comprised 22 (52.38%) cases, ALL 14 (33.33%) cases, and AL 6 (14.2%) cases. Normal karyotype was found in 18 (42.85%), abnormal karyotype in 16 (39.09%), and 8 (19.09%) were CF. Specific abnormalities of t(15;17), hyperdiploidy; t(3;3) with monosomy 7 in; del(9q22); del(2p); del(17p); del(Xq); 1~2 dmin; der(3); +11, +13 and composite karyotype. Hypodiploidy was strongly associated with AL, which signifies the loss of chromosomes causing potential risk. Composite karyotype, rare t(3;3) double minutes, +11,+13, del(9q), and del(Xq) were the novel findings reported in the South Canara region of Karnataka. Despite other molecular techniques, conventional cytogenetics remains the baseline in the diagnosis of malignancies.

A diagnostic approach to detect cytogenetic heterogeneity and its prognostic significance in multiple myeloma.

Objective: Multiple myeloma (MM) is a hematological disorder involving the uncontrolled proliferation of clonal plasma cells and its accumulation in the bone marrow. This study analyzed the frequency, cytogenetic heterogeneity, and clinical characteristics of patients with MM. Methods: Bone marrow aspirates were obtained from 72 patients with MM and evaluated by conventional cytogenetics (CCs) and interphase fluorescence in situ hybridization (iFISH) techniques for a panel of probes, including immunoglobulin heavy chain (IgH)/CCND1, IgH/fibroblast growth factor receptor 3 (FGFR3), IgH/MAFB, 13q deletion, and deletion 17p. Results: CCs revealed abnormal karyotypes in 39% of the patients examined. The incidence of hypodiploidy was 28% (20/72) while that of hyperdiploidy was 10% (7/72). iFISH analysis revealed t(11;14) in 6% (4/72) and t(4;14) in 11% (8/72) of patients. Patients with hyperdiploidy and hypodiploidy were associated with several monosomies and trisomies. Kaplan-Meier analysis revealed a significant difference between positive and negative groups for t(4;14), trisomy 14, and monosomy 13; this was associated with a shorter survival time. Cox proportional analysis identified t(4;14) (P = 0.032), trisomy 14 (P = 0.004), and monosomy 13 (P = 0.009), as significant factors with hazard ratio of 0.187 [confidence interval (CI): 0.041-0.862], 0.109 [CI: 0.024-0.500] and 0.134 [CI: 0.030-0.600]. Conclusion: In addition to cytogenetic abnormalities, iFISH analysis revealed significant heterogeneity among patients with MM. Cytogenetic heterogeneity in patients with MM should be considered as a major prognostic marker contributing to the variability of the disease. Our findings suggest that these abnormalities are independent prognostic factors.

Exploring breast cancer exosomes for novel biomarkers of potential diagnostic and prognostic importance.

The comprehensive bioinformatics analysis of breast cancer exosomes revealed that HSP90AA1, CCT2, and ENO1 were novel hub genes in the giant protein-protein interaction network of 110 exosomal proteins. Exosomes and their cargo such as discrete proteins, nucleic acids, and lipids are having potential role in the pathophysiology of breast cancer (BC). This study showed that the identified hub genes were particularly abundant in GO and KEGG pathways relevant to the positive regulation of telomerase. In addition, these hub genes were found to be considerably overexpressed in breast adenocarcinoma patients compared to healthy controls, and further, this overexpression is linked to the poor prognosis in BC patients. Furthermore, the ROC analysis revealed that CCT2 gene has strong diagnostic and prognostic value for BC. Additionally, this in silico analysis found that the anticancer agents and HSP90 inhibitors such as ganetespib, retaspimycin, and tanespimycin would have considerable potential in the treatment of BC. Overall, this study findings imply that HSP90AA1, a molecular chaperon and CCT2, a chaperonin would serve as diagnostic and prognostic biomarkers, respectively, for BC. However, these findings need to be further confirmed by laboratory and clinical studies for validating their potential applications. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03422-w.

Identification of key gene signatures and their characterization by expression correlation with drug sensitivity in smoking-associated oral squamous cell carcinoma.

AIMS: Oral squamous cell carcinoma (OSCC), a most frequent type of head-and-neck cancer, is becoming more common and posing a substantial health risk. Using a network biology strategy, this study intended to find and investigate critical genes associated with OSCC. MATERIALS AND METHODS: The extended protein-protein interaction networks for differentially expressed genes related to smoking and nonsmoking conditions of OSCC were constructed and visualized using Cytoscape software. The hub genes/proteins were determined based on degree and betweenness centrality measures and then evaluated and validated for expression using the Gene Expression Profiling Interactive Analysis 2 (GEPIA2), and their relationship to the sensitivity of small molecules was discovered utilizing the Gene Set Cancer Analysis (GSCA) web server. RESULTS: A total of 596 differentially expressed genes were screened, and four genes, interleukin (IL)-6, JUN, tumor necrosis factor (TNF), and vascular endothelial growth factor A (VEGFA), were identified as hub proteins, and their expression and overall survival in head-and-neck cancers were further investigated using GEPIA2. TNF and VEGFA gene expressions were considerably greater in cancers when compared to normal samples, while JUN and IL-6 gene expressions were not statistically significant. Further, these hub proteins are found to have a substantial favorable correlation with overall survival of head-and-neck cancer patients. Finally, GSCA was used to predict gene-specific potential drugs that act on these molecules by combining mRNA expression and drug sensitivity data from the Genomics of Drug Sensitivity in Cancer and the Cancer Therapeutics Response Portal. CONCLUSIONS: The hub genes/proteins identified in this study could help researchers better understand the molecular processes involved in the progression and metastasis of oral cancer in smokers.

Correlation of preferentially expressed antigen of melanoma (PRAME) gene expression with clinical characteristics in acute leukemia patients.

BACKGROUND: Preferentially expressed antigen of melanoma (PRAME) gene is regularly overexpressed in acute leukemia (AL) and other malignant diseases which are recognized by human leucocyte antigen (HLA-24) located in the human chromosome of 22q11 coded by 509 amino acids. To rule out the PRAME gene expression in AL patients and its correlation with clinical characteristics in the Indian population set up by RT-qPCR. RESULTS: A total of 42 samples collected, 29 (69.4%) were males, and 13 (30.95%) were females, with a mean and standard deviation for age were 39.07 ± 22.22 years. Of which AML were of 22 (52.38%) cases, ALL were of 14 (33.33%) cases, and 6 (14.2%) cases which included other forms of leukemia. PRAME gene expression was highly expressed in thirty-three 27 (64.28%) AL patients compared to the least expression in healthy individuals. No significant difference between the different forms of AL (p=0.3203) was observed. Cytogenetic analysis of normal karyotype (NK), abnormal karyotype (Ab. K), and culture failure (CF) displayed statistical non-significance (p=0.5801). Among cytogenetic abnormalities obtained, no significant differences between the groups were observed (p=0.8507). Chloride, potassium, and absolute lymphocyte count (ALC) was found to be statistically significant with p=0.0038**, p=0.0358*, and p=0.0216*, respectively, between all other clinical characteristics. There was no correlation between the PRAME gene expression and clinical parameters. CONCLUSION: PRAME gene expression in AL patients was highly expressed, comparable to studies reported globally with significant cytogenetic results. PRAME gene could be used as a potential diagnostic marker for monitoring the malignancies and minimal residual disease in AL.