Oncogenesis of multiple myeloma: 14q32 and 13q chromosomal abnormalities are not randomly distributed, but correlate with natural history, immunological features, and clinical presentation
Oncogenesis of multiple myeloma: 14q32 and 13q chromosomal abnormalities are not randomly distributed, but correlate with natural history, immunological features, and clinical presentation
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DOI：
10.1182/blood.v99.6.2185
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发表时间：
2002-03-15
期刊：
影响因子：
20.3
通讯作者：
Bataille, R
中科院分区：
文献类型：
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作者：
Avet-Loiseau, H;Facon, T;Bataille, R
多发性骨髓瘤（MM）是一种浆细胞恶性肿瘤，其特征在于显著的流行病学、生物学和临床异质性。这项研究的目的是找到这种异质性的遗传基础。使用荧光原位杂交技术，我们分析了901例患有各种浆细胞疾病的患者的前瞻性队列，包括意义不明的单克隆丙种球蛋白病、郁积型MM、MM和原发性浆细胞白血病，以确定涉及13 q14和14 q32染色体区域的遗传异常;这些患者连续参加Intergroupe Francophone du Myelome临床试验，我们进行了统计分析，比较这些染色体异常的免疫学（即免疫球蛋白类型和轻链亚型）和临床状态，并在一定程度上，预后特征。发现14 q32易位和del（13）是最常见的染色体异常，分别在75%和45%的患者中观察到，并且不是随机分布的，而是相互关联的。其次，它们之间的相关性使我们能够定义4种主要的患者遗传类别：（1）缺乏任何14 q32异常的患者（25%），通常也缺乏del（13）;（2）呈现t（4;14）或t（14;16）的患者，几乎总是与del（13）相关。（15%的患者）;（3）患有其他14 q32异常并出现del（13）的患者（25%）;和（4）患有其他14 q32异常但未出现del（13）的患者（35%）。第三，我们发现这种遗传分层与免疫状态和临床表现以及一些主要的预后因素高度相关。这项研究首次为MM患者中观察到的异质性提供了遗传学支持，并证明14 q32和13 q染色体异常不是随机分布的。我们发现的强相关性可能是MM的新遗传分类的基础，正如先前在白血病和淋巴瘤中所证明的那样。此外，我们的研究支持MM肿瘤发生的不同模型。
Multiple myeloma (MM) is a plasma-cell malignancy characterized by marked epidemiological, biological, and clinical heterogeneity. The goal of this study was to find a genetic basis for this heterogeneity. Using fluorescence in situ hybridization, we analyzed a prospective cohort of 901 patients with various plasma-cell disorders-monoclonal gammopathies of undetermined significance, smoldering MM, MM, and primary plasma-cell leukemia-for genetic abnormalities involving the 13q14 and 14q32 chromosomal regions; the patients were consecutively enrolled in the Intergroupe Francophone du Myelome clinical trials, We performed statistical analyses comparing these chromosomal abnormalities in terms of immunological (ie, immunoglobulin types and light-chain subtypes) and clinical status and, to some exent, prognostic features. It was found that 14q32 translocations and del(13) are the most frequent chromosomal abnormalities, observed in 75% and 45% of the patients, respectively, and are not randomly distributed, but interconnected. Second, correlations between them allowed us to define 4 major genetic categories of patients: (1) patients lacking any 14q32 abnormality (25%) and generally also lacking del(13); (2) patients presenting either t(4;14) or t(14;16), almost always associated with a del(13) (15% of patients); (3) patients with other 14q32 abnormalities and presenting del(13) (25%); and (4) patients with other 14q32 abnormalities but not presenting del(13) (35%). Third, we show that this genetic stratification is highly correlated with immunological status and clinical presentation and with some major prognostic factors. For the first time, this study gives genetic support to the heterogeneity observed in patients with MM and demontrates that the 14q32 and 13q chromosomal abnormalities are not randomly distributed. The strong correlations we found might be the basis for a novel genetic classification of MM, as has been previously demonstrated for leukemias and lymphomas. Furthermore, our study supports different models for MM oncogenesis.