Schofield D, West D C, Anthony D C, Marshal R, Sklar J
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
Am J Pathol. 1995 Feb;146(2):472-80.
Patients with the nevoid basal cell carcinoma syndrome (NBCCS) are at increased risk for medulloblastomas as well as for basal cell carcinomas. The gene for NBCCS has been mapped to chromosome 9q22.3-q31 by linkage analysis, and loss of heterozygosity (LOH) in this region has been demonstrated in approximately one-half of sporadic basal cell carcinomas. In the present study, LOH for chromosome 9q22.3-q31 microsatellite markers was investigated in medulloblastomas occurring among children with NBCCS and in sporadic medulloblastomas. Histologically, all 3 NBCCS medulloblastomas were noted to have a desmoplastic phenotype, and LOH was detected in both of the 2 cases for which microsatellite markers were heterozygous in normal tissues. LOH was also detected in a subset of sporadic medulloblastomas, each of which were found to display the desmoplastic phenotype. In all, 3 of the 6 sporadic desmoplastic tumors showed LOH, whereas LOH was not seen in any of the 11 sporadic, non-desmoplastic medulloblastomas studied. Additionally, desmoplastic tumors lacking detectable LOH each showed histological features of so-called cerebellar neuroblastoma, a subgroup of desmoplastic medulloblastoma with extensive neuroblastomatous differentiation. The data are consistent with a role for inactivation of a tumor suppressor gene at chromosome 9q in the development of medulloblastomas in patients with NBCCS and of sporadic medulloblastomas characterized by a desmoplastic phenotype similar to that found in patients with NBCCS. Restriction of chromosome 9q loss to non-neuroblastomatous desmoplastic tumors suggests that this variant of medulloblastoma maybe pathogenetically distinct from tumors having other histological phenotypes.
痣样基底细胞癌综合征（NBCCS）患者患髓母细胞瘤和基底细胞癌的风险增加。通过连锁分析，已将NBCCS基因定位于9号染色体的9q22.3 - q31区域，并且在大约一半的散发性基底细胞癌中已证实该区域存在杂合性缺失（LOH）。在本研究中，对NBCCS患儿中发生的髓母细胞瘤以及散发性髓母细胞瘤进行了9q22.3 - q31微卫星标记的杂合性缺失研究。组织学上，所有3例NBCCS髓母细胞瘤均具有促纤维增生型表型，在正常组织中微卫星标记为杂合的2例病例中均检测到了LOH。在一部分散发性髓母细胞瘤中也检测到了LOH，这些肿瘤均表现出促纤维增生型表型。总共6例散发性促纤维增生型肿瘤中有3例显示LOH，而在研究的11例散发性、非促纤维增生型髓母细胞瘤中均未发现LOH。此外，缺乏可检测到的LOH的促纤维增生型肿瘤均显示出所谓小脑神经母细胞瘤的组织学特征，小脑神经母细胞瘤是促纤维增生型髓母细胞瘤的一个亚组，具有广泛的神经母细胞瘤样分化。这些数据表明，9号染色体上一个肿瘤抑制基因的失活在NBCCS患者髓母细胞瘤以及具有与NBCCS患者相似促纤维增生型表型的散发性髓母细胞瘤的发生发展中起作用。9号染色体缺失局限于非神经母细胞瘤样促纤维增生型肿瘤，提示这种髓母细胞瘤变体在发病机制上可能与具有其他组织学表型的肿瘤不同。
