GERMLINE P53 GENE-MUTATIONS IN SUBSETS OF GLIOMA PATIENTS
GERMLINE P53 GENE-MUTATIONS IN SUBSETS OF GLIOMA PATIENTS
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DOI：
10.1093/jnci/86.5.344
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发表时间：
1994-03-02
影响因子：
10.3
通讯作者：
SAYA, H
中科院分区：
文献类型：
--
作者：
KYRITSIS, AP;BONDY, ML;SAYA, H
背景：在Li-Fraumeni综合征患者中，有时在非家族性恶性肿瘤如多灶性骨肉瘤中，在一小部分有两个或更多原发恶性肿瘤的年轻患者中，以及在散发性乳腺癌患者中，已经发现了P53基因的可遗传胚系突变。我们最近报道，多灶性胶质瘤经常与其他原发恶性肿瘤相关，我们假设这种现象可能是基因改变造成的。目的：我们研究了胶质瘤患者中胚系p53基因突变的频率，以及病变的多灶性、附加的原发(不同)恶性肿瘤病史或癌症家族史。方法：采用RNA-聚合酶链式反应、单链构象多态性分析和基因测序技术对51例脑胶质瘤患者的淋巴细胞进行p53基因突变分析。结果：19例多灶性脑胶质瘤患者中有6例检测到胚系p53基因突变，其中2例有癌症家族史，1例有原发恶性肿瘤家族史，2例有全部3种危险因素；4例单灶性胶质瘤患者中1例，另1例有原发恶性肿瘤家族史；15例单灶性胶质瘤患者中，2例有家族癌症史，但无二次恶性肿瘤史。在单灶性胶质瘤和其他恶性肿瘤患者中未检测到突变，在12例对照患者中未检测到突变，这些患者中没有第二种恶性肿瘤或癌症家族史。发生突变的患者比同一组中的其他患者年轻。结论：多灶性脑胶质瘤、脑胶质瘤和其他原发恶性肿瘤，以及与癌症家族史相关的脑胶质瘤患者中，胚系P53基因突变是常见的，尤其是当这些因素联合使用时。提示：高危亲属可以被确定为遗传咨询、早期癌症检测，以及可能参加化学预防试验。
Background: Heritable germline mutations of the p53 gene have been described in patients with Li-Fraumeni syndrome, occasionally in nonfamilial malignancies such as multifocal osteosarcoma, in a small subgroup of young patients with two or more primary malignancies, and in patients with sporadic breast carcinoma. We recently reported that multifocal gliomas are frequently associated with other primary malignancies, and we hypothesized that genetic alterations may account for this phenomenon. Purpose: We examined the frequency of germline p53 gene mutations in patients with glioma and either multifocality of lesions, history of an additional primary (different) malignancy, or a family history of cancer. Methods: Lymphocytes from 51 glioma patients were analyzed for germline p53 gene mutations using RNA-polymerase chain reaction analysis, single-strand conformation polymorphism, and gene sequencing techniques. Results: Germline p53 gene mutations were detected in six of 19 patients with multifocal glioma, including two with family history of cancer, one with another primary malignancy, and two with all three risk factors; one of four patients with unifocal glioma, another primary malignancy, and a family history of cancer; and two of 15 patients with unifocal glioma and a family history of cancer but no second malignancies. No mutations were detected in the patient with unifocal glioma and another malignancy or in the 12 control patients with unifocal glioma and no second malignancies or family history of cancer. Patients having mutations were younger than other patients in the same group. Conclusions: Germline p53 mutations are frequent in patients with multifocal glioma, glioma and another primary malignancy, and glioma associated with a family history of cancer, particularly if these factors are combined. Implications: Relatives at high risk can be identified for genetic counseling, early cancer detection, and possible enrollment in chemoprevention trials.