Vortmeyer A O, Stavrou T, Selby D, Li G, Weil R J, Park W S, Moon Y W, Chandra R, Goldstein A M, Zhuang Z
Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland 20892, USA.
Cancer. 1999 Jun 15;85(12):2662-7.
Medulloblastomas can occur sporadically or may be associated with hereditary tumor syndromes including familial adenomatous polyposis (FAP) and nevoid basal cell carcinoma syndrome (NBCCS).
The authors performed a retrospective analysis for allelic deletion of the adenomatous polyposis coli (APC) and PTCH gene loci using paraffin embedded medulloblastoma specimens from patients who were admitted to Children's National Medical Center in Washington, DC, between 1982 and 1997. Thirty-five cases from which tumor and normal tissue could be procured were analyzed. Two of the analyzed cases had a positive family and personal history for NBCCS; in both cases the histology of the medulloblastoma revealed a desmoplastic phenotype. Thirty-three cases were not known to be associated with hereditary disease; 2 of those cases revealed desmoplastic and 31 cases revealed nondesmoplastic "classic" medulloblastoma histology.
Although medulloblastoma tumorigenesis has been associated strongly with FAP associated with APC germline mutation, none of the 22 informative sporadic cases revealed loss of heterozygosity of the APC gene locus. PTCH gene deletion was detected in the tumors of both patients with NBCCS. In contrast, only 1 of 33 sporadic medulloblastomas revealed PTCH gene deletion. The sporadic case with PTCH gene deletion did not demonstrate the desmoplastic phenotype.
In conjunction with previous studies, the data from the current study confirm that allelic deletion occurs in NBCCS-associated medulloblastomas, consistent with the role of PTCH as a tumor suppressor gene. However, in sporadic medulloblastomas, allelic deletion of PTCH is an infrequent event. Morphologic examination in conjunction with genetic analysis of PTCH gene deletion in medulloblastoma tissue may prove to be a quick and efficient test with which to screen for NBCCS in patients with medulloblastomas. Although medulloblastoma is a component of Turcot syndrome with demonstrated APC mutations, APC gene deletions appear to be absent or very uncommon in patients with sporadic and NBCCS-associated medulloblastomas.
髓母细胞瘤可散发发生，或与遗传性肿瘤综合征相关，包括家族性腺瘤性息肉病（FAP）和痣样基底细胞癌综合征（NBCCS）。
作者对1982年至1997年间入住华盛顿特区儿童国家医疗中心的患者的石蜡包埋髓母细胞瘤标本进行了腺瘤性息肉病大肠杆菌（APC）和PTCH基因座等位基因缺失的回顾性分析。分析了35例可获取肿瘤组织和正常组织的病例。其中2例分析病例有NBCCS的阳性家族史和个人史；这两例病例中髓母细胞瘤的组织学均显示为促结缔组织增生型。33例病例未知与遗传性疾病相关；其中2例显示为促结缔组织增生型，31例显示为非促结缔组织增生型“经典”髓母细胞瘤组织学。
尽管髓母细胞瘤的发生与与APC种系突变相关的FAP密切相关，但22例信息丰富的散发性病例中均未发现APC基因座杂合性缺失。在两名NBCCS患者的肿瘤中均检测到PTCH基因缺失。相比之下，3３例散发性髓母细胞瘤中仅1例显示PTCH基因缺失。PTCH基因缺失的散发性病例未表现出促结缔组织增生型表型。
结合先前的研究，本研究的数据证实NBCCS相关的髓母细胞瘤中发生等位基因缺失，这与PTCH作为肿瘤抑制基因的作用一致。然而，在散发性髓母细胞瘤中，PTCH等位基因缺失是罕见事件。髓母细胞瘤组织中PTCH基因缺失的形态学检查结合基因分析可能是一种快速有效的检测方法，用于筛查髓母细胞瘤患者中的NBCCS。尽管髓母细胞瘤是Turcot综合征的一个组成部分且已证实存在APC突变，但APC基因缺失在散发性和NBCCS相关的髓母细胞瘤患者中似乎不存在或非常罕见。
