{"title":"Cytogenetic Abnormalities in Multiple Myeloma: Incidence, Prognostic Significance, and Geographic Heterogeneity in Indian and Western Populations.","authors":"Pratibha Kadam Amare, Shraddha Nikalje Khasnis, Pranita Hande, Hrushikesh Lele, Nishigandha Wable, Snehal Kaskar, Nikita Nikam Gujar, Nikhil Gardi, Aniket Prabhudesai, Karishma Todi, Rohit Waghole, Pritha Roy","doi":"10.1159/000529191","DOIUrl":null,"url":null,"abstract":"<p><p>Multiple myeloma (MM) is a genetically complex and heterogeneous neoplasm in which cytogenetics is a major factor playing an important role in the risk stratification of disease. High-risk MM based upon cytogenetic classification includes primary IGH translocations t(4;14), t(14;16), t(14;20), and secondary progressive aberrations such as gain/amp(1q), 1p deletion, del(17p), and hypodiploidy. Several studies have proved that interphase FISH can detect primary as well as secondary cryptic aberrations very efficiently in lowest 5-10% abnormal plasma cell population. The present large-scale study was undertaken to evaluate the incidence of cytogenetic abnormalities, to analyse the correlation of conventional karyotyping with FISH, and to seek the geographic heterogeneity in the incidence of primary as well as secondary aberrations in our Indian versus Western populations. We conducted prospective studies of 1,104 patients consecutively referred from the primary, secondary, and tertiary oncology centres from all over India. Interphase FISH was performed on isolated plasma cells. Karyotype analysis was done as per ISCN 2016 and 2020. FISH could detect cytogenetic abnormalities in 67.6% of the cases with an incidence of 59% non-hyperdiploidy. The incidence of IGH translocation was 26% versus literature frequency of 40-50% which was mainly due to a low incidence (6%) of t(11;14) in contrast to 15-20% in other series. Additionally, the association of secondary progressive aberrations in the hyperdiploid group rather than the non-hyperdiploid group in our patients is not a common finding. A biallelic inactivation of TP53 as an ultra-high risk factor was detected in old-aged patients. These observations disclose the novel findings and strongly indicate the racial disparity which leads to geographic heterogeneity. In contrast to FISH, conventional karyotyping could detect MM-related aberrations in 50% of cases, of which 44% revealed highly complex karyotypes with common aberrations of chromosome 1q. Overall, FISH was found to be a novel, easy approach with high success rate and capability of detection of all cytogenetic abnormalities that add valid information for the risk stratification of disease. This, in future, in combination with mutation profile and gene expression profile will help in further refinement of disease and identification of actionable targets.</p>","PeriodicalId":11206,"journal":{"name":"Cytogenetic and Genome Research","volume":null,"pages":null},"PeriodicalIF":1.7000,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10534967/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cytogenetic and Genome Research","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1159/000529191","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/2/13 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Multiple myeloma (MM) is a genetically complex and heterogeneous neoplasm in which cytogenetics is a major factor playing an important role in the risk stratification of disease. High-risk MM based upon cytogenetic classification includes primary IGH translocations t(4;14), t(14;16), t(14;20), and secondary progressive aberrations such as gain/amp(1q), 1p deletion, del(17p), and hypodiploidy. Several studies have proved that interphase FISH can detect primary as well as secondary cryptic aberrations very efficiently in lowest 5-10% abnormal plasma cell population. The present large-scale study was undertaken to evaluate the incidence of cytogenetic abnormalities, to analyse the correlation of conventional karyotyping with FISH, and to seek the geographic heterogeneity in the incidence of primary as well as secondary aberrations in our Indian versus Western populations. We conducted prospective studies of 1,104 patients consecutively referred from the primary, secondary, and tertiary oncology centres from all over India. Interphase FISH was performed on isolated plasma cells. Karyotype analysis was done as per ISCN 2016 and 2020. FISH could detect cytogenetic abnormalities in 67.6% of the cases with an incidence of 59% non-hyperdiploidy. The incidence of IGH translocation was 26% versus literature frequency of 40-50% which was mainly due to a low incidence (6%) of t(11;14) in contrast to 15-20% in other series. Additionally, the association of secondary progressive aberrations in the hyperdiploid group rather than the non-hyperdiploid group in our patients is not a common finding. A biallelic inactivation of TP53 as an ultra-high risk factor was detected in old-aged patients. These observations disclose the novel findings and strongly indicate the racial disparity which leads to geographic heterogeneity. In contrast to FISH, conventional karyotyping could detect MM-related aberrations in 50% of cases, of which 44% revealed highly complex karyotypes with common aberrations of chromosome 1q. Overall, FISH was found to be a novel, easy approach with high success rate and capability of detection of all cytogenetic abnormalities that add valid information for the risk stratification of disease. This, in future, in combination with mutation profile and gene expression profile will help in further refinement of disease and identification of actionable targets.
期刊介绍:
During the last decades, ''Cytogenetic and Genome Research'' has been the leading forum for original reports and reviews in human and animal cytogenetics, including molecular, clinical and comparative cytogenetics. In recent years, most of its papers have centered on genome research, including gene cloning and sequencing, gene mapping, gene regulation and expression, cancer genetics, comparative genetics, gene linkage and related areas. The journal also publishes key papers on chromosome aberrations in somatic, meiotic and malignant cells. Its scope has expanded to include studies on invertebrate and plant cytogenetics and genomics. Also featured are the vast majority of the reports of the International Workshops on Human Chromosome Mapping, the reports of international human and animal chromosome nomenclature committees, and proceedings of the American and European cytogenetic conferences and other events. In addition to regular issues, the journal has been publishing since 2002 a series of topical issues on a broad variety of themes from cytogenetic and genome research.