Lo Cunsolo C, Iolascon A, Cavazzana A, Cusano R, Strigini P, Mazzocco K, Giordani L, Massimo L, De Bernardi B, Conte M, Tonini G P
Unit of Solid Tumor Biology Advanced Biotechnology Center, Genoa, Italy.
Cancer Genet Cytogenet. 1999 Mar;109(2):126-30. doi: 10.1016/s0165-4608(98)00154-x.
Familial neuroblastoma occurs rarely. We studied a family with three children; one of them has a disseminated (stage 4) and another has a localized (stage 2) neuroblastoma. We observed subtelomeric locus D1Z2 (1p36) deletion in both tumors by using double-color fluorescence in situ hybridization. The MYNC gene was found in single copy in both tumors. Loss of heterozygosity (LOH) and restriction fragment length polymorphism analyses were performed by using DNA from frozen tumor cells and from microdissected tumor areas excised from paraffin-embedded sections. We detected somatic LOH at locus D1S468 (1p36) in a tumor-cell population with a trisomy 1 of the stage-2 patient. Neuroblastoma cells of the stage-4 patient were diploid and showed allelic loss at the following loci: D1S172, D1S80, D1S94, D1S243, D1S468, D1S214, D1S241, and D1S164. Haplotype study showed that the siblings inherited the same paternal 1p36-->pter chromosome region by homologous recombination and that, in the two tumors, arm 1p of different chromosomes of maternal origin was damaged. Our results suggest that the siblings inherited the predisposition to neuroblastoma associated with paternal 1p36 region and that tumors developed as a consequence of somatic loss of the maternal 1p36 allele.
家族性神经母细胞瘤很少见。我们研究了一个有三个孩子的家庭；其中一个患有播散性（4期）神经母细胞瘤，另一个患有局限性（2期）神经母细胞瘤。我们通过双色荧光原位杂交在两种肿瘤中观察到亚端粒位点D1Z2（1p36）缺失。在两种肿瘤中均发现MYNC基因呈单拷贝。利用来自冷冻肿瘤细胞以及从石蜡包埋切片中切除的显微切割肿瘤区域的DNA进行杂合性缺失（LOH）和限制性片段长度多态性分析。在一名2期患者的肿瘤细胞群体中，我们检测到1号染色体三体时D1S468（1p36）位点存在体细胞杂合性缺失。4期患者的神经母细胞瘤细胞为二倍体，并在以下位点显示等位基因缺失：D1S172、D1S80、D1S94、D1S243、D1S468、D1S214、D1S241和D1S164。单倍型研究表明，这对兄弟姐妹通过同源重组继承了相同的父源1p36→pter染色体区域，并且在这两种肿瘤中，母源不同染色体的1p臂均受到损伤。我们的结果表明，这对兄弟姐妹继承了与父源1p36区域相关的神经母细胞瘤易感性，并且肿瘤是由于母源1p36等位基因的体细胞缺失而发生的。
