Lynch H T, Sanger W G, Pirruccello S, Quinn-Laquer B, Weisenburger D D
Department of Preventive Medicine, Creighton University School of Medicine, Omaha, NE 68178, USA.
J Natl Cancer Inst. 2001 Oct 3;93(19):1479-83. doi: 10.1093/jnci/93.19.1479.
The etiology of multiple myeloma (MM) remains obscure, although reports of familial clustering have implicated both a host susceptibility factor and environmental effects. Here we describe the medical histories of members of a family prone to MM.
We developed a pedigree for an MM-prone family by using information obtained from a questionnaire. Protein immunoelectrophoresis of serum and urine from the proband and from 19 family members was performed to detect monoclonal immunoproteins. Peripheral blood obtained from the proband and from five relatives was subjected to standard cytogenetic studies to detect constitutional chromosomal abnormalities. Multifluor-fluorescence in situ hybridization (M-FISH) and standard FISH studies were performed on peripheral blood from the proband and from two other affected living relatives to determine their karyotypes and to detect clonal chromosomal abnormalities frequently seen in patients with MM.
Within this family, a sibship of seven included three individuals (including the proband) with histologically verified MM and two individuals with a monoclonal gammopathy of unknown significance (MGUS), as determined by immunoelectrophoresis of serum and urine. This family also had members with acute lymphocytic leukemia, malignant melanoma, and prostate cancer. In the family members tested, we detected no constitutional chromosomal abnormality. None of the three individuals analyzed by FISH had a deletion of the retinoblastoma (Rb-1) locus, which is frequently deleted in patients with MM, and only one (the proband) had a translocation involving chromosomes 11 and 14, a clonal abnormality commonly seen in MM.
The study of familial MM may provide insights into the pathogenesis and, ultimately, the control and prevention of MM and related disorders.
尽管有家族聚集性的报道提示宿主易感性因素和环境影响均与多发性骨髓瘤（MM）的病因有关，但其病因仍不明确。在此，我们描述一个易患MM的家族成员的病史。
通过问卷调查获得的信息，我们绘制了一个易患MM家族的系谱图。对先证者及19名家族成员的血清和尿液进行蛋白免疫电泳，以检测单克隆免疫蛋白。对先证者及五名亲属的外周血进行标准细胞遗传学研究，以检测染色体结构异常。对先证者及另外两名在世的患病亲属的外周血进行多荧光原位杂交（M-FISH）和标准FISH研究，以确定其核型，并检测MM患者中常见的克隆性染色体异常。
在这个家族中，一个七口之家有三名个体（包括先证者）经组织学证实患有MM，两名个体经血清和尿液免疫电泳确定患有意义未明的单克隆丙种球蛋白病（MGUS）。这个家族还有患急性淋巴细胞白血病、恶性黑色素瘤和前列腺癌的成员。在接受检测的家族成员中，我们未检测到染色体结构异常。通过FISH分析的三名个体中，无一例存在MM患者中常见的视网膜母细胞瘤（Rb-1）基因座缺失，只有一名（先证者）存在涉及11号和14号染色体的易位，这是MM中常见的克隆性异常。
对家族性MM的研究可能为MM及相关疾病的发病机制以及最终的控制和预防提供见解。
