Work

The CCND1 c.870G risk allele is enriched in individuals of African ancestry with plasma cell dyscrasias

Year: 2020

Type: article

Abstract: Plasma cell (PC) dyscrasias, including multiple myeloma (MM), represent a spectrum of monoclonal gammopathies resulting from a clonal expansion of an abnormal plasma cell clone 1 . MM is generally preceded by precursor conditions known as monoclonal gammopathy of undetermined significance (MGUS) and smoldering MM (SMM) and is the most common hematologic malignancy in African Americans (AAs) 2 , 3 . It has been established that AAs, including Ghanaian men, display a 2–3-fold higher prevalence of MGUS with a reported similar risk of MGUS to MM progression compared to European Americans (EAs) 4 , 5 , 6 . An increased MM incidence has also been observed in individuals with a family history of MM, an effect that was greater for individuals who self-identify as black 7 , suggesting that constitutional, MM susceptibility risk allele/s may explain the increased prevalence of MGUS among individuals of African ancestry. Interestingly, AAs also appear to have either a similar or in some cases superior survival outcome compared to EAs depending on patient age, specific treatment modalities and access to care including clinical trial enrollment 3 , 8 , 9 , 10 . This disparity in outcome may be explained by genetic differences that predispose to specific acquired, cytogenetically defined subtypes, which can influence disease prognosis and response to treatment. These cytogenetic subtypes can be broadly classified into either hyperdiploid (characterized by gains of odd-numbered chromosomes) or translocations involving the immunoglobulin heavy chain ( IgH ) gene on chromosome 14. In the context of MM, hyperdiploidy and translocations t(11;14)(q13;q32) and t(6;14)(p21;q32) are typically associated with a favorable prognosis, while translocations t(4;14)(p16;q32), t(14;16)(q32;q23), or t(14;20)(q32;q12) translocations are generally associated with an unfavorable prognosis 1 .

Source: Blood Cancer Journal

DOI: 10.1038/s41408-020-0294-5