RB蛋白的表达与喉鳞癌的相关性

目的研究恶性视网膜母细胞瘤(RB)蛋白的表达与喉鳞癌的相关性。方法采用免疫组化(ABC)法检测43例喉鳞癌患者手术标本中RB蛋白的表达。结果RB蛋白的表达阳性率为44．2%;RB蛋白的表达与肿瘤的T分期、病理分级、5年生存期、肿瘤的原发部位无明显的相关性(P>0．05),但与淋巴结转移有关(P<0．05)。结论细胞调控周期中CyclinD1、RB、P16、CDK4等因素在喉鳞癌的发生发展中可能起着协同作用,而并非主要由于RB基因的突变和缺失造成细胞癌变。     

A novel translocation t(11;13) (q21;q14.2) in a child with suprasellar primitive neuroectodermal tumor and retinoblastoma

Purpose: To report on a novel translocation related to a suprasellar primitive neuroectodermal tumor (sPNET) and retinoblastoma.

Design: Case report.

Methods: A 6-year-old girl underwent genetic testing after developing unilateral retinoblastoma subsequent to treatment (surgery, chemotherapy, and stem-cell rescue) for a sPNET found at 1 year of age.

Results: Genetic testing found the girl’s karyotype to be 46,XX,t(11;13)(q21;q14.2); a novel translocation not previously reported in patients with either retinoblastoma or sPNET.

Conclusions: Our patient had a novel translocation affecting the retinoblastoma 1 (RB1) gene, 46,XX,t(11;13)(q21;q14.2) resulting in the late development of unilateral retinoblastoma. Although she only developed unilateral retinoblastoma, her central nervous system was affected at a very early age. How her complex mutation resulted in retinoblastoma and antecedent sPNET remains unknown.     

Spectrum of RB1 Mutations in Argentine Patients: 20-years Experience in the Molecular Diagnosis of Retinoblastoma

ABSTRACT

Background: Retinoblastoma is a hereditary cancer of childhood caused by mutations in the RB1 tumor suppressor gene. An early diagnosis is critical for survival and eye preservation, thus identification of RB1 mutations is important for unequivocal diagnosis of hereditary retinoblastoma and risk assessment in relatives.

Methods: We studied 144 families for 20 years, performing methodological changes to improve detection of mutation. Segregation analysis of polymorphisms, MLPA, FISH and cytogenetic assays were used for detection of “at risk haplotypes” and large deletions. Small mutations were identified by heteroduplex/DNA sequencing.

Results: At risk haplotypes were identified in 11 familial and 26 sporadic cases, being useful for detection of asymptomatic carriers, risk exclusion from relatives and uncovering RB1 recombinations. Ten large deletions (eight whole gene deletions) were identified in six bilateral/familial and four unilateral retinoblastoma cases. Small mutations were identified in 29 cases (four unilateral retinoblastoma patients), being the majority nonsense/frameshift mutations. Genotype-phenotype correlations confirm that the retinoblastoma presentation is related to the type of mutation, but some exceptions may occur and it is crucial to be considered for genetic counseling. Three families included second cousins with retinoblastoma carrying different haplotypes, which suggest independent mutation events.

Conclusion: This study enabled us to obtain information about molecular and genetic features of patients with retinoblastoma in Argentina and correlate them to their phenotype.     

Synchronous small cell carcinoma and adenocarcinoma of the lung representing different retinoblastoma tumor suppressor protein status

We report a case of synchronous primary lung cancers —small cell carcinoma and adenocarcinoma. We analyzed the expression of neuropeptides and tumor suppressor gene products in the two carcinomas, using immunohistochemistry. The small cell carcinoma showed absence of retinoblastoma (RB) tumor suppressor protein and the presence of neural differentiation-related protein, while the adenocarcinoma showed expression of RB protein with nuclear localization and the absence of neural protein. These results indicate that different carcinogenic steps may have been involved in the development of small cell carcinoma and adenocarcinoma in this patient.     

膀胱癌人乳头瘤病毒感染与Ha-ras、p53、RB基因变异及其临床意义的研究

采用分子杂交、PCR-SSCP技术检测了39例膀胱癌及7例正常膀胱组织中HPV16、18感染及Ha-ras、p53、RB基因变异,并结合临床分期、病理分级等参数进行了综合分析.结果表明,膀胱癌组织中HPV16、18感染率及Ha-ras、p53、RB基因变异率分别为61.5%、36%、30.8%及15.4%;HPV阳性率与分级分期、p53基因突变与HPV感染呈明显负相关;Ha-ras、p53基因突变率与分级分期正相关,其中Ha-ras基因在复发肿瘤的突变率显著高于原发肿瘤;部分标本同时呈HPV感染与p53基因突变、Ha-ras与p53基因突变.提示高危HPV感染和Ha-ras、p53、RB基因变异及相互作用在很大程度上参与了膀胱癌的发生及演变,并与其生物学行为密切相关,有望成为判断肿瘤恶性程度、自然病程及预后的估价指标.     

应用FISH技术检测慢性淋巴细胞白血病ATM 和RB1基因缺失*

目的：探讨慢性淋巴细胞白血病（CLL）中11q22.3（ATM基因）和13q14（RB1 基因）的缺失情况以及荧光原位杂交（fluorescence in situ hybridization,FISH）技术检测慢性淋巴细胞白血病（CLL）染色体异常的价值,了解CLL 的分子遗传学特性。方法：分别用ATM和RB1 探针,运用荧光原位杂交（FISH）技术对10例CLL 确诊患者的11q22.3 和13q14染色体进行检测,并和常规细胞遗传学（Conventional cytogenetics,CC）检测方法,即G 显带法进行比较。结果：10例CLL 患者常规细胞遗传学检出2 例,其中t（5,9）,t（10,12）和+ 12各1 例;而FISH方法检出7 例至少有一种分子遗传学异常,del（11q22.3）4 例,纯合缺失2 例,del（13q14）7例,纯合缺失2 例。10例患者中4 例同时有del（11q22.3）和del（13q14）这2 种染色体异常。结论：FISH是一种在分析CLL 染色体异常方面较为快速、准确和敏感的有效技术,可提高染色体异常检出率,为CLL 提供较为准确的分子细胞遗传学信息,指导临床与预后分析。     

人脑胶质瘤与SV40的关系及其p53、RB蛋白的表达

目的：探讨人脑胶质瘤与猴病毒４０（ＳＶ４０）的关系及其ｐ５３和ＲＢ蛋白的表达。方法：采用核酸原位杂交和免疫组织化学技术对２５６例人脑胶质瘤和１１例正常脑组织进行了ＳＶ４０ ＤＮＡ和抑癌基因产物ｐ５３、ＲＢ蛋白检测。结果：胶质瘤ＳＶ４０阳性１０４例,阳性率４０．６％,正常脑组织均未检测出ＳＶ４０ ＤＮＡ,未发现ＳＶ４０感染与胶质瘤病理分级存在明显相关（Ｐ〉０．０５）;ＳＶ４０阳性胶质瘤ｐ５３、ＲＢ蛋     

乙肝病毒/黄曲霉毒素双暴露因素下肝癌13号染色体畸变以及RB1基因表达的初步研究

目的探讨乙肝病毒/黄曲霉毒素双暴露下肝细胞性肝癌(hepatocellular carcinoma,HCC)13号染色体遗传学改变的特点,以及对定位于13q14.2基因座位点抑癌基因RB1的影响。方法 32例手术切除且经病理证实为HCC的癌组织,按照乙肝病毒与黄曲霉毒素的暴露情况,分为4个亚组:A组HBV(+)/AFB1(+)10例;B组HBV(+)/AFB1(-)10例;C组HBV(-)/AFB1(+)6例;D组HBV(-)/AFB1(-)6例。应用微阵列比较基因组杂交技术(ArrayCGH)检测包括13号染色体在内的23对染色体区段的变化情况,并通过RT-PCR检测RB1mRNA的表达情况。结果 32例中有15例染色体13q14.2发生缺失,缺失率为46.9%(15/32)。13q14.2缺失的发生频率在A组、B组、C组、D组中分别为80.0%(8/10)、50.0%(5/10)、33.3%(2/6)和0%(0/6)。其中A组分别与C组、D组比较,差异具有统计学意义(P<0.05);B组与D组比较,差异亦有统计学意义(P<0.05)。RT-PCR检测显示RB1mRNA的表达半定量灰度值在13q14.2缺失组中显著低于13q14.2无缺失组(P=0.003)。结论染色体13q畸变在HCC中是一个常见的分子生物学事件,其中13q14.2的缺失可能与HBV和AFB1双暴露的协同作用有关,HCC中13q14.2的缺失是导致RB1基因失活的因素之一。