Gafanovich A, Ramu N, Krichevsky S, Pe'er J, Amir G, Ben-Yehuda D
Hematology Department, Hadassah University Hospital, Jerusalem, Israel.
Cancer. 1999 Jan 15;85(2):504-10.
The past decade has witnessed a growing frequency of therapy-related secondary tumors. The authors studied nine children with secondary malignancies. The primary tumors were bilateral retinoblastoma, neuroblastoma, brain tumor, Wilms' tumor, colon adenocarcinoma, and Hodgkin's disease. The secondary tumors were osteosarcoma at the site of previous radiotherapy, myelodysplastic syndrome, acute myelocytic leukemia, glioblastoma, thyroid carcinoma, and B-cell lymphoma.
DNA was extracted from the primary and secondary tumors and analyzed for genetic alterations in the p53 gene and in 7 separate microsatellites.
The authors found p53 mutations in 7 patients, loss of heterozygosity in 1 patient, and both mutation and loss of heterozygosity in 1 patient. Mutations were demonstrated in the primary tumors only in two patients and in the secondary tumors only in three patients. Two patients had a mutation in both the primary and the secondary tumor; in both patients the two mutations were in different exons. Microsatellite instability (MIN) was identified in five to seven loci in the secondary tumors of all patients.
The observed MIN is compatible with the presence of a mutator phenotype that predisposes these children to the development of secondary malignancies.
在过去十年中，与治疗相关的继发性肿瘤的发生频率日益增加。作者对9例继发性恶性肿瘤患儿进行了研究。原发性肿瘤包括双侧视网膜母细胞瘤、神经母细胞瘤、脑肿瘤、肾母细胞瘤、结肠腺癌和霍奇金病。继发性肿瘤为先前放疗部位的骨肉瘤、骨髓增生异常综合征、急性髓细胞白血病、胶质母细胞瘤、甲状腺癌和B细胞淋巴瘤。
从原发性和继发性肿瘤中提取DNA，分析p53基因和7个独立微卫星的基因改变。
作者发现7例患者存在p53突变，1例患者存在杂合性缺失，1例患者同时存在突变和杂合性缺失。仅在2例患者的原发性肿瘤中发现突变，仅在3例患者的继发性肿瘤中发现突变。2例患者的原发性和继发性肿瘤均有突变；在这2例患者中，两个突变位于不同的外显子。在所有患者的继发性肿瘤中，在5至7个位点发现了微卫星不稳定性（MIN）。
观察到的MIN与一种突变表型相符，这种突变表型使这些儿童易患继发性恶性肿瘤。
