Paraf F, Jothy S, Van Meir E G
Service d'Anatomie Pathologique, Hôpital Universitaire Dupuyten, Limoges, France.
J Clin Oncol. 1997 Jul;15(7):2744-58. doi: 10.1200/JCO.1997.15.7.2744.
This report presents a comprehensive and statistical analysis of the brain tumor-polyposis (BTP) cases referred to as Turcot's syndrome in the literature.
BTP patients encompass a heterogeneous group that can be classified into two statistically distinct clinical entities based on phenotype of the polyps (P = .0001), presence of colorectal cancer (P = .0001), type of brain neoplasm, ie, glioma or medulloblastoma (P = .0001), presence of skin lesions (P = .0004) and cafe-au-lait spots (P = .0008), as well as consanguinity (P = .0135).
The first entity (BTP syndrome type 1) consists of patients who have glioma and colorectal adenomas without polyposis (non-FAP cases), and their siblings with glioma and/or colorectal adenomas. For these patients, we show that the patient's age at malignant glioma occurrence is less than 20 years (50 to 80 years in the general population), which strongly supports the existence of an underlying genetic cause. The neoplasms of these patients show DNA replication errors, which suggests a relationship with hereditary nonpolyposis colorectal cancer (HNPCC), a disease characterized by germline alterations in DNA mismatch repair genes. The second entity (BTP syndrome type 2) consists of patients with a CNS tumor that occurs in a familial adenomatous polyposis kindred (FAP cases). These patients carry germline mutations in the APC gene, which suggests that mutations in this gene might predispose to brain tumors. Risk analysis shows increased incidence of medulloblastoma in FAP patients, but APC mutations are not found in sporadic glioma or medulloblastoma. Therefore, further investigations should establish whether the occurrence of medulloblastoma in an FAP family represents a variant of FAP.
本报告对文献中称为Turcot综合征的脑肿瘤-息肉病（BTP）病例进行了全面的统计分析。
BTP患者是一个异质性群体，根据息肉的表型（P = 0.0001）、结直肠癌的存在情况（P = 0.0001）、脑肿瘤的类型，即胶质瘤或髓母细胞瘤（P = 0.0001）、皮肤病变的存在情况（P = 0.0004）和咖啡牛奶斑（P = 0.0008）以及近亲结婚情况（P = 0.0135），可分为两个在统计学上有显著差异的临床实体。
第一个实体（BTP综合征1型）包括患有胶质瘤和无息肉病的结肠腺瘤（非FAP病例）的患者，以及患有胶质瘤和/或结肠腺瘤的他们的兄弟姐妹。对于这些患者，我们发现恶性胶质瘤发生时患者的年龄小于20岁（普通人群为50至80岁），这有力地支持了潜在遗传病因的存在。这些患者的肿瘤显示出DNA复制错误，这表明与遗传性非息肉病性结直肠癌（HNPCC）有关，HNPCC是一种以DNA错配修复基因种系改变为特征的疾病。第二个实体（BTP综合征2型）包括在家族性腺瘤性息肉病家族（FAP病例）中发生中枢神经系统肿瘤的患者。这些患者携带APC基因的种系突变，这表明该基因的突变可能易患脑肿瘤。风险分析显示FAP患者中髓母细胞瘤的发病率增加，但在散发性胶质瘤或髓母细胞瘤中未发现APC突变。因此，进一步的研究应确定FAP家族中髓母细胞瘤的发生是否代表FAP的一种变体。
