Kadam Amare Pratibha, Nikalje Khasnis Shraddha, Hande Pranita, Lele Hrushikesh, Wable Nishigandha, Kaskar Snehal, Nikam Gujar Nikita, Gardi Nilesh, Prabhudesai Aniket, Todi Karishma, Waghole Rohit, Roy Pritha
Oncocytogenetics and Oncomolecular Department, Lilac Insights Pvt. Ltd, Navi Mumbai, India.
ACTREC, Tata Memorial Center, Navi Mumbai, India.
Cytogenet Genome Res. 2022;162(10):529-540. doi: 10.1159/000529191. Epub 2023 Feb 13.
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.
多发性骨髓瘤（MM）是一种基因复杂且异质性的肿瘤，其中细胞遗传学是疾病风险分层中起重要作用的主要因素。基于细胞遗传学分类的高危MM包括原发性IGH易位t(4;14)、t(14;16)、t(14;20)，以及继发性进展性畸变，如1q获得/扩增、1p缺失、17p缺失和亚二倍体。多项研究证明，间期荧光原位杂交（FISH）能够在低至5%-10%的异常浆细胞群体中非常有效地检测原发性以及继发性隐匿性畸变。本大规模研究旨在评估细胞遗传学异常的发生率，分析传统核型分析与FISH的相关性，并探寻印度人群与西方人群中原发性及继发性畸变发生率的地域异质性。我们对来自印度各地一级、二级和三级肿瘤中心连续转诊的1104例患者进行了前瞻性研究。对分离出的浆细胞进行间期FISH检测。核型分析按照国际人类细胞遗传学命名法（ISCN）2016和2020版进行。FISH在67.6%的病例中检测到细胞遗传学异常，其中非超二倍体的发生率为59%。IGH易位的发生率为26%，而文献报道的频率为40%-50%，这主要是由于t(ll;14)的发生率较低（6%），而其他系列报道的发生率为15%-20%。此外，在我们的患者中，超二倍体组而非非超二倍体组出现继发性进展性畸变的关联并不常见。在老年患者中检测到TP53双等位基因失活作为超高危因素。这些观察结果揭示了新的发现，并强烈表明种族差异导致了地域异质性。与FISH相比，传统核型分析在50%的病例中能检测到与MM相关的畸变，其中44%显示出高度复杂的核型，伴有常见的1号染色体q臂畸变。总体而言，FISH被发现是一种新颖、简便的方法，成功率高，能够检测所有细胞遗传学异常，为疾病风险分层提供有效信息。这在未来与突变谱和基因表达谱相结合，将有助于进一步完善疾病诊断并确定可操作的靶点。
