背景:多发性骨髓瘤(MM)是一种异质性血液恶性肿瘤,其特征是骨髓中恶性浆细胞的克隆性扩增。该病伴有各种临床表现,比如骨损伤,贫血,高钙血症,和肾功能不全。然而,尽管过去二十年来治疗取得了重大进展,这种疾病仍然难以治疗,大多数病人都会复发.虽然其发病机制尚未阐明,很明显,基因组不稳定在其发展或对治疗的抵抗中起着关键作用.在某些情况下,这种不稳定的原因是染色体,一种复杂的基因组重排形式,涉及在单个灾难性事件中染色体的破碎和随后的随意重组。由此产生的重新安排涉及各种结构变化,包括删除,重复,倒置,和易位,导致基因组破坏。具体来说,这些变化可能导致肿瘤抑制基因(TP53和CDKN2C)的改变或失活,癌基因的激活(MAF,FGFR3和CCND1)或参与关键细胞过程的基因。解开导致色素沉着的机制提供了鉴定MM发病机理中涉及的关键基因和途径的机会。这些发现可以作为改进的非诊断方法的基础。
目的:本综述的目的是总结MM中常见的原发性和继发性染色体畸变,特别着重于引入复杂的染色体畸变,尤其是MM中的染色体。
BACKGROUND: Multiple myeloma (MM) is a heterogeneous hematological malignancy characterized by clonal expansion of malignant plasma cells in the bone marrow. The disease is accompanied by various clinical manifestations, such as bone lesions, anemia, hypercalcemia, and renal insufficiency. However, despite significant advances in treatment over the last two decades, the disease remains challenging to treat, and most patients relapse. Although its pathogenesis has not yet been elucidated, it is clear that genomic instability plays a key role in its develop-ment or resistance to treatment. In some instances, the cause of this instability is
chromothripsis, a form of complex genomic rearrangement that involves shattering and subsequent haphazard reassembly of chromosomes within a single catastrophic event. The resulting rearrangements involve a variety of structural changes, including deletions, duplications, inversions, and translocations, that lead to genome disruption. Specifically, these changes may result in alteration or inactivation of tumor suppressor genes (TP53 and CDKN2C), activation of oncogenes (MAF, FGFR3, and CCND1) or genes involved in key cellular processes. Unraveling the mechanisms that result in
chromothripsis provides opportunities to identify critical genes and pathways involved in MM pathogenesis. These findings may serve as a basis for improved dia-gnostic approaches.
OBJECTIVE: The goal of this review is to summarize the common primary and secondary chromosomal aberrations in MM with a particular focus on introducing complex chromosomal aberrations, especially
chromothripsis in MM.