Matsumoto T, Kinoshita E, Maeda H, Niikawa N, Kurosaki N, Harada N, Yun K, Sawai T, Aoki S, Kondoh T
Department of Pediatrics, Nagasaki University School of Medicine, Japan.
Jpn J Hum Genet. 1994 Jun;39(2):225-34. doi: 10.1007/BF01876842.
We described a patient with Beckwith-Wiedemann syndrome associated with rhabdomyosarcoma (RMS), and renal cell carcinoma (RCC). Karyotypes of peripheral lymphocytes and RMS cells were normal. DNA analyses showed maternal loss of heterozygosity (LOH) at 11p15 region in RMS but not in RCC. The insulin-like growth factor II gene (IGF2) was found to be expressed at a moderate level in RMS but not in RCC by in situ hybridization. Each of parental allele-derived IGF2 transcript was detected in RCC, while maternal allele-derived transcript was weak in RMS because of maternal LOH. These results suggest that (1) loss of imprinting (LOI) of IGF2 might be responsible for BWS, (2) on the other hand, LOI itself might not induce tumor occurrence in tissues where the control of tissue-specific expression of IGF2 is maintained, (3) increased expression of IGF2 due to maternal loss of a putative controller gene for IGF2 at 11p15 might predispose to sustaining tumorigenic mutations and tumor progression, (4) loss of a putative onco-suppressor gene at 11p15 might induce RMS occurrence. The cause of RCC was thought to be different from that of RMS.
我们描述了一名患有贝克威思-维德曼综合征并伴有横纹肌肉瘤（RMS）和肾细胞癌（RCC）的患者。外周血淋巴细胞和RMS细胞的核型均正常。DNA分析显示，RMS中11p15区域存在母源杂合性缺失（LOH），而RCC中未出现。通过原位杂交发现，胰岛素样生长因子II基因（IGF2）在RMS中呈中等水平表达，而在RCC中不表达。在RCC中检测到了来自每个亲本等位基因的IGF2转录本，而由于母源LOH，RMS中来自母源等位基因的转录本较弱。这些结果表明：（1）IGF2的印记丢失（LOI）可能与BWS有关；（2）另一方面，在维持IGF2组织特异性表达调控的组织中，LOI本身可能不会诱导肿瘤发生；（3）由于11p15处IGF2假定调控基因的母源缺失导致IGF2表达增加，可能易患持续性致瘤突变和肿瘤进展；（4）11p15处假定的抑癌基因缺失可能诱导RMS发生。RCC的病因被认为与RMS不同。
