Kyritsis A P, Bondy M L, Xiao M, Berman E L, Cunningham J E, Lee P S, Levin V A, Saya H
Department of Neuro-Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
J Natl Cancer Inst. 1994 Mar 2;86(5):344-9. doi: 10.1093/jnci/86.5.344.
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.
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.
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.
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.
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.
Relatives at high risk can be identified for genetic counseling, early cancer detection, and possible enrollment in chemoprevention trials.
李-佛美尼综合征患者中已发现p53基因的遗传性种系突变，偶尔也见于非家族性恶性肿瘤，如多灶性骨肉瘤、一小部分患有两种或更多原发性恶性肿瘤的年轻患者以及散发性乳腺癌患者。我们最近报道多灶性胶质瘤常与其他原发性恶性肿瘤相关，我们推测基因改变可能是这一现象的原因。
我们研究了患有胶质瘤且有病变多灶性、额外原发性（不同）恶性肿瘤病史或癌症家族史的患者中种系p53基因突变的频率。
采用RNA聚合酶链反应分析、单链构象多态性和基因测序技术，对51例胶质瘤患者的淋巴细胞进行种系p53基因突变分析。
19例多灶性胶质瘤患者中有6例检测到种系p53基因突变，其中2例有癌症家族史，1例有另一种原发性恶性肿瘤，2例具备所有三个风险因素；4例单灶性胶质瘤、有另一种原发性恶性肿瘤且有癌症家族史的患者中有1例；15例单灶性胶质瘤且有癌症家族史但无第二种恶性肿瘤的患者中有2例。单灶性胶质瘤合并另一种恶性肿瘤的患者以及12例单灶性胶质瘤且无第二种恶性肿瘤或癌症家族史的对照患者未检测到突变。发生突变的患者比同组其他患者年轻。
种系p53突变在多灶性胶质瘤、胶质瘤合并另一种原发性恶性肿瘤以及与癌症家族史相关的胶质瘤患者中很常见，特别是这些因素同时存在时。
可以识别出高风险亲属进行遗传咨询、早期癌症检测，并可能纳入化学预防试验。
