幼儿着色性干皮病伴角化棘皮瘤1例

患儿,男,18个月。面部起红斑、褐色斑片、结节1年余。病理诊断为着色性干皮病伴角化棘皮瘤。     

DNA修复基因XPA在非小细胞肺癌中的表达及其临床意义

目的:分析非小细胞肺癌(NSCLC)组织中DNA修复基因Xeroderma Pigmentosum Group A(XPA)的表达状况及其与临床病理特征的关系。方法:采用免疫组织化学方法(IHC)检测初治中晚期NSCLC患者癌组织中XPA的表达状况,采用χ2检验比较各亚组之间的XPA表达状况的差异。结果:109例NSCLC组织中XPA的阳性表达率为55.0%(60/109),其表达与性别、吸烟史有密切关系,在男性组中的阳性率(61.0%)显著高于女性组(37.0%)(P=0.030);吸烟组的XPA阳性率显著高于不吸烟组(分别为68.1%和45.2%,P=0.017);但在吸烟人群中,吸烟量不同的亚组间XPA的表达率未见明显差异。XPA阳性率在不同年龄、临床TNM分期、组织学类型或分化程度、淋巴结转移和远处转移亚组中的差异均无统计学意义(均P>0.05)。结论:XPA在NSCLC组织中的表达状况与性别、吸烟状况密切相关,并可能与NSCLC的发生有关。     

XPD和P53对HepG2.2.15增殖及乙型肝炎病毒X蛋白表达的影响

目的:探讨人着色性干皮病基因D(XPD)和P53对人肝癌细胞株HepG2.2.15增殖及乙型肝炎病毒X蛋白(HBx)、Bcl-2和Bax基因表达的影响.方法:用脂质体转染法将重组质粒pEGFP-N2/XPD和空载质粒pEGFP-N2转染HepG2.2.15细胞,转染后第2天给予20 μmol/L的Pifithrin-α(P53抑制剂)孵育24h.分为空白对照组、pEGFP-N2组、pEGFP-N2/XPD组、pEGFP-N2/XPD+Pifithrin-α组及Pifithrin-α组.用RT-PCR和Western blotting方法检测XPD、HBx、Bcl-2和Bax表达的变化;用MTT法观察细胞增殖活力;用流式细胞仪检测细胞周期.结果:(1)重组质粒pEGFP-N2/XPD的转染使得XPD表达增高(均P＜0.001);XPD表达增高使得HBx和Bcl-2表达降低,同时使得Bax表达增高,而Pifithrin-α能抑制XPD这一作用(均P＜0.01).(2)XPD表达增高抑制了细胞增殖活力,而Pifithrin-α能抑制XPD降低细胞活力的作用(均P＜0.001).(3)XPD表达增高引起了细胞G1期增加、S期减少,而Pifithrin-α能抑制XPD这一作用(均P ＜0.001).结论:XPD是通过P53途径抑制肝癌细胞增殖,下调HBx和Bcl-2的表达并上调Bax的表达;XPD、P53和HBx三者之间能相互作用、相互影响,共同调节肝癌的发生与发展.     

De Sanctis-Cacchione Syndrome in a female infant - Case report

The De Sanctis-Cacchione Syndrome is the rarest and most severe kind of xeroderma pigmentosum, characterized by microcephaly, hypogonadism, neurological disorders, mental and growth retardation, with very few cases published. The clinical findings compatible with De Sanctis-Cacchione Syndrome and the therapeutic approach used to treat a one year and nine months old child, with previous diagnosis of xeroderma pigmentosum, are reported.     

Regulation of the specialized DNA polymerase eta: Revisiting the biological relevance of its PCNA‐ and ubiquitin‐binding motifs

During translesion synthesis (TLS), low‐fidelity polymerases of the Y‐family polymerases bypass DNA damages that block the progression of conventional processive DNA polymerases, thereby allowing the completion of DNA replication. Among the TLS polymerases, DNA polymerase eta (polη) performs nucleotide incorporation past ultraviolet (UV) photoproducts and is deficient in cancer‐prone xeroderma pigmentosum variant (XPV) syndrome. Upon UV irradiation, the DNA sliding clamp PCNA is monoubiquitylated on its conserved Lys‐164. This event is considered to facilitate the TLS process in vivo since polη preferentially interacts with monoubiquitylated PCNA through its ubiquitin‐binding domain (UBZ) as well as its PCNA interacting peptide (PIP)‐box. However, recent observations questioned this model. Therefore, in this study, we re‐examined the relative contribution of the regulatory UBZ and PIP domains of polη in response to UVC. We show that simultaneous invalidation of both motifs confers sensitivity to UVC, sensitization by low concentrations of caffeine, prolonged inhibition of DNA synthesis and persistent S phase checkpoint activation, all characteristic features of XPV cells. While each domain is essential for efficient accumulation of polη in replication factories, mutational inactivation of UBZ or PIP motif only confers a slight sensitivity to UVC indicating that, although informative, polη focus analysis is not a reliable tool to assess the polη's ability to function in TLS in vivo. Taken together, these data indicate that PIP and UBZ motifs are not required for recruitment but for retention of polη at sites of stalled replication forks. We propose that this is a way to ensure that a sufficient amount of the protein is available for its bypass function. Environ. Mol. Mutagen., 2012. © 2012 Wiley Periodicals, Inc.     

Effect of Xeroderma Pigmentosum Complementation Group FPolymorphisms on Gastric Cancer Risk and Associations withH.pylori Infection

We conducted a hospital case-control study by genotyping four potential functional single nucleotidepolymorphisms (SNPs) to assess the association of Xeroderma pigmentosum complementation group F (XPF)with gastric cancer susceptibility, and role of XPF polymorphisms in combination with H.pylori infection in riskdefinition. A total of 331 patients with gastric cancer and 355 controls were collected. Four SNPs of XPF, rs180067,rs1799801, rs2276466 and rs744154, were genotyped by Taqman real-time PCR method with a 7900 HT sequencedetector system. The gastric cancer patients were more likely to have smoking habit, a family history of cancerand H.pylori infection. We did not find any significant difference in the genotype distributions of XPF rs180067,rs1799801, rs2276466 and rs744154 between cases and controls. However, multivariate logistic analysis showeda non-significant decreased risk in patients carrying rs180067 G allele, rs1799801 T allele or rs2276466 T allelegenotypes. A non-significant increased risk of gastric cancer was found in individuals carrying the rs744154 GGgenotype. Stratification by H.pylori infection and smoking was not significantly different in polymorphisms ofXPF rs180067, rs1799801, rs2276466 and rs744154. The four XPF SNPs did not show significant interaction withH.pylori infection and smoking status (P for interaction was 0.35 and 0.18, respectively). Our study indicatedthat polymorphisms in rs180067, rs1799801, rs2276466 and rs744154 may affect the risk of gastric cancer butfurther large sample size studies are needed to validate any association.     

Association of XPG rs2094258 polymorphism with gastric cancer prognosis

BACKGROUND The xeroderma pigmentosum group G(XPG)gene at chromosome 13q33 consists of 15 exons,which may be related to the occurrence and development of gastric cancer(GC).AIM To examine the association of several common single nucleotide polymorphisms(SNPs)of the XPG gene with GC risk and survival.METHODS Five SNPs of XPG(rs2094258,rs751402,rs873601,rs2296147,and rs1047768)were genotyped by PCR restriction fragment length polymorphism in 956 histologically confirmed GC cases and 1012 controls in North China.GC patients were followed for survival status and,if deceased,cause of death.Logistic regression and Cox regression were used for analysing associations of XPG SNPs with risk of GC and prognosis,respectively.For rs2094258,heterozygous model(CT vs CC),homozygous model(TT vs CC),recessive model(TT vs CT+CC),and dominant model(TT+CT vs CC)were analyzed.RESULTS None of the examined loci were statistically associated with GC risk,although rs2296147 was marginally associated with GC risk(P=0.050).GC patients with the rs2094258 CT+CC genotype showed worse survival than those with the TT genotype(log-rank test,P=0.028),and patients with the CC genotype had a tendency of unfavourable prognosis compared with those with the TT+CT genotype(log-rank test,P=0.039).The increase in C alleles of rs2094258[hazard ratio(HR)=1.19,95%confidence interval(CI):1.02-1.45,P=0.037]were associated with the long-term survival of GC cases.Other risk factors for survival included tumor differentiation(HR=4.51,95%CI:1.99-8.23,P<0.001),lymphovascular invasion(HR=1.97,95%CI:1.44-3.01,P<0.001),and use of chemotherapy(HR=0.81,95%CI:0.63-0.98,P=0.041).CONCLUSION The XPG rs2094258 polymorphism may be associated with overall survival in GC patients.     

Orbital amelanotic melanoma in xeroderma pigmentosum: a rare association

Xeroderma pigmentosum (XP) is an autosomal recessive genetic disorder of DNA repair in which the body's normal ability to repair damage caused by ultraviolet light is deficient. This leads to a 1000-fold increased risk of cutaneous and ocular neoplasms. Ocular neoplasms occurring in XP in order of frequency are squamous cell carcinoma, basal cell carcinoma and melanoma. Malignant melanomas occur at an early age in patients with XP. We report a case of XP with massive orbital melanoma in an eight-year-old boy which is unique due to its amelanotic presentation confirmed histopathologically.     

Ophthalmic manifestations and histopathology of xeroderma pigmentosum: two clinicopathological cases and a review of the literature

Xeroderma pigmentosum is a rare, autosomal recessive disease caused by a defect in DNA repair. Patients with xeroderma pigmentosum often have cutaneous and ocular sun sensitivity, freckle-like skin pigmentation, multiple skin and eye cancers, and, in some patients, progressive neurodegeneration. Xeroderma pigmentosum predominantly affects the ultraviolet (UV) exposed ocular surface, resulting in eyelid atrophy and cancers, corneal dryness, exposure keratopathy, and conjunctival tumors. We report the clinical history and ocular pathology of two white women who had xeroderma pigmentosum with neurological degeneration: Case 1 (died at age 44 years) and Case 2 (died at age 45 years). Case 1, with mutations in the XPA gene, had more than 180 basal cell carcinomas of her skin and eyelids and died from complications of neurodegeneration. Case 2, with mutations in the XPD gene, was sun-protected and had three skin cancers. She died from complications of neurodegeneration and pneumonia. Both patients had bilateral pinguecula, corneal pannus, and exposure keratopathy. Case 1 had bilateral optic atrophy, and Case 2 had bilateral peripheral retinal pigmentary degeneration. Both patients developed retinal gliosis. The ophthalmic manifestations and pathology of xeroderma pigmentosum are discussed and reviewed with respect to this report and other cases in the literature. These cases illustrate the role of DNA repair in protection of the eyes from UV damage and neurodegeneration of the retina.