P53 GENE ALTERATIONS IN X-RAYED TINEA CAPITIS PATIENTS

X 射线检查的头癣患者中的 P53 基因改变

• 批准号: 2733165
• 负责人: FREDRIC Jay Burns
• 金额: $ 29.33万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-30 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2733165
• 关键词: DNA; DNA damage; X ray; cancer risk; chemical fingerprinting; chromosome translocation; gene deletion mutation; human genetic material tag; human subject; neoplasm /cancer epidemiology; neoplasm /cancer genetics; nucleic acid sequence; polymerase chain reaction; prognosis; radiation related neoplasm /cancer; single strand conformation polymorphism; skin neoplasms; southern blotting; tinea; tumor suppressor genes

The ongoing epidemiological study of about 2000 x-radiated tinea capitis patients and 1400 controls is providing evidence that x-irradiation in childhood causes a significant increase (relative risk = 3.7 for single tumors and = 8.0 for multiple tumors) in the incidence of basal cell carcinomas (BCCs). Other evidence suggests Uv light also plays a role, possibly as a promoter of x-ray initiated tumors, although Uv may also act as an tumor initiator by producing DNA damage in the form of CC to TT or C to T base changes. Some patients in the tinea study exhibit evidence of substantially higher than normal risk of a skin cancers. The heightened risk is apparent in patients who have already developed a cancer; the risk of a second cancer is roughly 40% per 5 years versus only about 2% per 5 years for those without a prior cancer. A preliminary study of skin tumors from the x-irradiated patients showed evidence of possible x-ray damage to the p53 gene; 5 of 6 BCCs or epitheliomas exhibited deletion or translocation damage to exons 7, 8 or 9, and 1 of 6 patients showed a total p53 deletion in DNA from blood leukocytes. The research proposed here is designed to answer the following questions raised by the initial findings in this unique patient population: 1. How closely are the genetic changes in the p53 gene of the induced cancers linked to the probable etiologic agent (UV or x-ray), 2. are p53 gene alterations as measured in blood leukocytes of high cancer risk patients a possible genetic basis for their increased susceptibility, and 3. are multiple skin cancers on the same patient derived from distinct and independent genetic lesions. Skin cancers presenting in the clinic will be removed and examined histologically. Tumor DNA will be extracted and analyzed by polymerase chain reaction (PCR) as a way to quantity major internal deletions and other rearrangements, while SSCP followed by DNA sequencing will be used to identify base pair alterations. DNA fingerprinting techniques will be used to establish whether multiple cancers on the same patient are genetically distinct. Specific exon probes will be utilized to on Southern blots to distinguish small deletions from translocations. The proposed work will establish the types and incidence of p53 gene alterations in radiation-induced skin BCCs and whether the type of p53 alteration is predictive of the response to secondary prevention by topical 5-fluorouracil.

正在进行的约2000例X射线辐射性脑炎的流行病学研究 患者和1400名对照者提供的证据表明， 儿童期导致显著增加（相对风险= 3.7， 对于多发性肿瘤，≥ 8.0）的基底细胞癌发生率 癌（BCC）。其他证据表明紫外线也起了作用， 可能作为X射线引发的肿瘤的促进剂，尽管UV也可能 通过以CC的形式产生DNA损伤， TT或C到T碱基的变化。 在这项研究中， 有证据表明患皮肤癌的风险远高于正常风险。的 在已经发展成 癌症;第二种癌症的风险大约是每5年40%， 对于那些没有癌症病史的人来说，每5年只有2%。初步 对X射线照射患者皮肤肿瘤的研究显示， p53基因可能存在X射线损伤; 6例基底细胞癌或上皮瘤中有5例 表现出外显子7、8或9的缺失或易位损伤，以及 6例患者血白细胞DNA中p53基因全部缺失。的 这里提出的研究旨在回答以下问题 在这个独特的患者群体中的初步发现提出：1.如何 与诱导的癌症中p53基因的遗传变化密切相关 与可能的病原体（UV或X射线）有关，2. p53基因 在高癌症风险患者的血液白细胞中测量的变化 一个可能的遗传基础，为他们增加的易感性，和3。是 同一患者的多种皮肤癌来自不同的 独立的遗传损伤皮肤癌在临床上表现将 取出并进行组织学检查。将提取肿瘤DNA， 通过聚合酶链反应（PCR）进行分析，作为主要的定量方法 内部缺失和其他重排，而SSCP随后是DNA 测序将用于鉴定碱基对改变。DNA 指纹技术将用于确定是否有多个 同一个病人身上的癌症在基因上是不同的。 特异性外显子 探针将用于Southern印迹以区分小的 易位的缺失。拟议的工作将建立类型 和辐射诱导的皮肤基底细胞癌中p53基因改变的发生率， p53改变的类型是否预测了对 局部用5-氟尿嘧啶进行二级预防。