Genomic studies of multiple myeloma reveal an association between X chromosome alterations and genomic profile complexity

Abstract

The genomic profile of multiple myeloma (MM) has prognostic value by dividing patients into a good prognosis hyperdiploid group and a bad prognosis nonhyperdiploid group with a higher incidence of IGH translocations. This classification, however, is inadequate and many other parameters like mutations, epigenetic modifications, and genomic heterogeneity may influence the prognosis. We performed a genomic study by array-based comparative genomic hybridization on a cohort of 162 patients to evaluate the frequency of genomic gains and losses. We identified a high frequency of X chromosome alterations leading to partial Xq duplication, often associated with inactive X (Xi) deletion in female patients. This partial X duplication could be a cytogenetic marker of aneuploidy as it is correlated with a high number of chromosomal breakages. Patient with high level of chromosomal breakage had reduced survival regardless the region implicated. A higher transcriptional level was shown for genes with potential implication in cancer and located in this altered region. Among these genes, IKBKG and IRAK1 are members of the NFKB pathway which plays an important role in MM and is a target for specific treatments. © 2016 Wiley Periodicals, Inc.

Recent advances in cytogenetic characterization of multiple myeloma

“…Hyperdiploidy is detected in about 50% cases of newly diagnosed MM and preferentially involves gain of the odd-numbered chromosomes 3,5,7,9,11,15,19, and 21. 16 It is considered a primary cytogenetic event in MM.…”

“…However, the low mitotic index, especially in the early stage of diseases, and a difficult interpretation of some cryptic aberrations can be main limiting factors. [4][5][6][7] Fluorescence in situ hybridization (FISH) or microarray-based technologies can overcome some of those drawbacks and detect specific target arrangements as well as chromosomal copy number changes. In this review, we will discuss different cytogenetic approaches and compare their strength and weakness to provide genetic information for risk stratification and prediction of outcome in MM patients.…”

“…Abnormal karyotypes are identified in about 30%‐50% of MM cases, more often in an advanced stage or a more proliferative form of diseases. However, the low mitotic index, especially in the early stage of diseases, and a difficult interpretation of some cryptic aberrations can be main limiting factors 4,5,6,7. Fluorescence in situ hybridization (FISH) or microarray‐based technologies can overcome some of those drawbacks and detect specific target arrangements as well as chromosomal copy number changes.…”

“…In this review, we will discuss different cytogenetic approaches and compare their strength and weakness to provide genetic information for risk stratification and prediction of outcome in MM patients. [7][8][9]…”

Multiple myeloma with extramedullary plasmacytoma: pathogenesis and clinical case

“…При ММ описаны мутации раковотестикулярных антигенов, расположенных на Ххромосоме [46]. В недавней ра боте бельгийских авторов, включившей 162 пациента с ММ, выявлена высокая частота изменений Ххро мосомы (полная или частичная делеция Ххромосомы обнаружена у 47 и 17 % пациентов соответственно) [47]. Важно отметить, что в регионе Xq28 расположены гены IKBKG и IRAK1, участвующие в NFκB -сигнальном пути, играющем ключевую роль в патогенезе ММ.…”