肝外胆管癌染色体3p21.3区段微卫星不稳定和杂合性缺失分析

目的:研究肝外胆管癌染色体3p21.3区段的微卫星不稳定性(MSI)及杂合性缺失(LOH),探讨染色体3p21.3区段遗传不稳定性与肝外胆管癌的发生发展的关系,定位该区段上肝外胆管癌相关肿瘤基因。方法:用PCR-SSCP方法检测24例肝外胆管癌染色体3p21.3区段上D3S1568,D3S1621,D3S1578和D3S1289四个微卫星位点的MSI和LOH发生率,分析其与临床病理因素之间的关系。结果:24例肝外胆管癌组织中,四个微卫星位点的MSI和LOH平均发生率分别为7.23%和15.63%。其中D3S1621位点的LOH最高(45.83%,11/24),并与TNM分期、是否伴有局部/淋巴结转移相关(p<0.05)。结论:染色体3p21.3区段D3S1621位点高频率杂合性缺失,提示3p21.3区段可能定位有肝外胆管癌的候选抑癌基因,并在肝外胆管癌的发生发展过程中发挥重要作用。     

Microsatellite alteration at chromosome 11 in primary human nasopharyngeal carcinoma in Taiwan.

Nasopharyngeal carcinoma (NPC) is one of the common cancers in Taiwan but is rare in western countries. The development of NPC involves multiple genetic changes in tumorigenesis and progression of the disease. To better understand genetic alterations in chromosome 11 which occur in human (NPC), we examined tumor specimens and corresponding non-cancerous tissue from 30 cases of NPC, using five microsatellite polymorphic markers whose location has previously been defined. To determine the clinical characteristics of MSI(+) or LOH, we performed correlation analysis of the findings with clinicopathological parameters. Loss of heterozygosity (LOH) was identified in 18 (60%) of 30 cases on at least one of the five markers. A high frequency of LOH was found at the two loci: D11S912 (7/30, 23.33%) and D11S934 (6/30, 20.00%), both of which are located within 11q23-24. We also found that 14 specimens (14/30, 46.67%) exhibited microsatellite instability (MSI(+)). Five (5/30, 16.67%) specimens exhibited MSI(+) in the transformation growth factor beta receptor type II (TGF-beta RII) exon 3 which also exhibited on chromosome 11. LOH was found to be significantly correlated with the T (tumor size) value (P=0.022) of Ho's system. MSI(+) showed a significant correlation with the N (lymph node) value of the UICC system (P=0.031). Our results suggest that multiple putative tumor suppressor genes on chromosome 11 play a role in the development of NPC. MSI(+) expression showed a predisposition to occur in the late stage of NPC while LOH tended to occur in early stages of NPC. The behavior of mutated TGF-beta RII exon 3, which appeared to serve as a dysfunction brake during nasopharyngeal carcinogenesis, may be a target gene in the defected mismatch repair system.     

Characterization of genetic alteration patterns in human esophageal squamous cell carcinoma using selected microsatellite markers spanning multiple loci

In order to identify representative genetic alterations in esophageal squamous cell carcinomas (ESCC) and useful markers for future early detection, 34 ESCC samples with neighboring normal epithelia and 30 esophageal biopsy samples from Linzhou, P.R. China, were studied. Of the 38 microsatellite markers selected, half were linked with tumor suppressors. More than 40% of the tumor samples showed loss of heterozygosity (LOH) in at least one of the eight markers, D3S1067 and D3S1561 (both linked to hMLH1 locus), FABP2, D4S1613, D9S171 (p14ARF, p15INK4b, p16INK4a loci), Rb1 (intron), p53-2 (intron), and NM23-H1. Most of the 38 microsatellite markers did not display microsatellite instability (MSI) in more than 30% of the tumor samples, except D9S942 (p14ARF, p15INK4b, p16INK4a loci) and Bat26, which showed frequency at 32 and 41%, respectively. Of all the ESCC samples examined, 20 samples exhibited LOH in 25% or more of the informative markers. Three samples displayed MSI in more than 30% of the markers, indicating that MSI might be an important event in these subset ESCC cases. Statistically significant correlations were found between LOH of the hMLH1 locus and the general LOH status of the sample, and between the LOH of the hMLH1 locus and p53 mutations. In addition, correlation was found between MSI in D3S1067/D3S1561 and the general MSI status in the samples. However, MSI in the introns of hMLH1 and hMSH2 were not correlated with the general MSI status of the tumors. LOH analysis was also performed in 30 esophageal biopsy samples containing precancerous lesions with matching blood samples using nine microsatellite markers selected from the above studies. LOH frequence ranged from 0 to 33% in informative cases, mostly in the 9p21 and p53 gene regions, suggesting these regions are possible targets of genomic instability in early stage ESCC carcinogenesis. The results demonstrate the degree of genetic alterations at different loci of the chromosomes. Some of the microsatellite markers may be useful for the early detection of ESCC.     

肝细胞癌8号染色体微卫星变异的研究

目的　　探讨肝细胞癌(HCC)8号染色体微卫星变异的特点及其与临床病理的相关性。方法采用MegaBACE　500型自动化DNA分析系统,对56例HCC中8号染色体上10个微卫星的杂合性缺失(LOH)、微卫星不稳定性(MSI)和等位基因失衡(AI)3种变异特征进行检测。结果　　56 例HCC 在8 号染色体上10 个基因座发生LOH 的总频率为66.1%(37 /56),MSI 的频率为12.5%(7 /56),AI的频率为19.6%(11/56)。LOH以D8S261最高为53.5%(23/43),其次为D8S1721(52.5%)和D8S1771(52.5%)。D8S277基因座,血清HBsAg阳性患者的LOH频率显著高于HBsAg阴性者(P<0.01),D8S261、D8S298和D8S1733基因座,血清HBsAg阴性患者的LOH频率显著高于HBsAg阳性者(P<0.01);D8S298和D8S1771基因座,肿瘤直径>3cm的LOH率明显高于￣<3cm组(P<0.05和P<0.01);在D8S1721基因座,无包膜或包膜不完整的肿瘤的LOH显著高于包膜完整的肿瘤(P<0.01);D8S298和D8S1771基因座,肝内转移者的LOH明显高于无肝内转移者(P<0.05)。MSI和AI与HCC临床病理学特点无明显相关性。结论　　HCC的8号染色体上存在广泛的微卫星变异,其中以代表肿瘤抑制基因路径的LOH方式在HCC的发生和发展过程中起重要作用,代表错配修复基因路径的MSI的作用次之。特定基因座的LOH与临床和病理学参数有一定的相关性。     

肝细胞癌8号染色体微卫星变异的研究(英文)

目的探讨肝细胞癌(HCC)8号染色体微卫星变异的特点及其与临床病理的相关性。方法采用 MegaBACE 500型自动化 DNA 分析系统,对56例 HCC 中8号染色体上10个微卫星的杂合性缺失(LOH)、微卫旱不稳定性(MSI)和等位基因失衡(AI)3种变异特征进行检测。结果 56例 HCC 在8号染色体上10个基因座发生 LOH 的总频率为66.1%(37/56),MSI 的频率为12.5%(7/56),AI 的频率为19.6%(11/56)。LOH 以 D8S261最高为53.5%(23/43),其次为 D8S1721(52.5%)和 D8S1771(52.5%)。D8S277基因座,血清HBsAg 阳性患者的 LOH 频率显著高于 HBsAg 阴性者(P<0.01),D8S261、D8S298和 D8S1733基因座,血清 HBsAg 阴性患者的 LOH频率显著高于 HBsAg 阳性者(P<0.01);D8S298和 D8S1771基因座.肿瘤直径>3cm 的 LOH 率明显高于≤3cm 组(P<0.05和 P<0.01);在 D8S1721基因座,无包膜或包膜不完整的肿瘤的 LOH 显著高于包膜完整的肿瘤(P<0.01);D8S298和 D8S1771基因座,肝内转移者的 LOH 明显高于无肝内转移者(P<0.05)。MSI 和 AI 与 HCC 临床病理学特点无明显相关性。结论 HCC 的8号染色体上存在广泛的微卫星变异,其中以代表肿瘤抑制基因路径的 LOH 方式在 HCC 的发生和发展过程中起重要作用,代表错配修复基因路径的 MSI 的作用次之。特定基因座的 LOH 与临床和病理学参数有一定的相关性。     

Loss of heterozygosity at the short arm of chromosome 3 in microdissected cervical intraepithelial neoplasia

Loss of heterozygosity (LOH) is a common genetic finding in many human neoplasms, including cervical cancer. The detection of LOH at specific loci in the precursor of cervical cancer, cervical intraepithelial neoplasia (CIN) may help in elucidating the evolution of this cancer, which has a clearly defined histological premalignant phase. However, molecular genetic investigation of CIN is difficult because many of the lesions are very small and sometimes ill defined topographically. In this study we analyzed eighteen polymorphic microsatellite repeats on chromosome 3p in CINs using a method of primer extension pre-amplification (PEP) for whole genome amplification combined with microdissection. These markers encompass chromosome region 3pter-3p12. LOH at one or more loci was detected in five (33%) out of the 15 informative cases with low grade CIN (CIN 1), while 22 (92%) out of 24 cases with high grade CIN (CIN 2 and 3) (P<0.01). The highest incidence (41%) of LOH was detected at locus D3S1038 (3p26.1-3p25.2). Frequent LOH (more than 20%) was also found at other loci including D3S1110 (3p25.3-3p25.1) (31%), D3S656 (3p25.1) (24%), D3S1076 (3p21.2-3p21.1) (29%), D3S1300 (3p21.1-3p14.2) (24%), D3S1600 (3p14.2-3p14.1) (24%), and D3S1079 (3p13) (25%). The results from this study taken together with others indicate that the genetic alterations on chromosome 3p are common in high grade of CIN and are probably early events in cervical carcinogenesis. Tumor suppressor gene(s) that play a role in cervical neoplasm may be located on the short arm of chromosome 3, likely at or near 3p26.1-25.1, 3p21.2-21.1, and 3p14.2-13.     

鼻咽癌染色体9p21～22区域精细缺失图谱的构建

目的 进一步精细限定鼻咽癌９ｐ２１－２２区域等位基因杂合性丢失的频率和范围,为发现和分离克隆该区域内的鼻咽癌抑瘤提供新线索和依据。方法 应用１１个定位于９ｐ－２１－２２区域的高密度微卫星位点,检测２５例低分化鼻咽癌患者的杂合性丢失。结果 ２５例患者中,有１７例存在一个或多个位点的杂合性丢失,占６８．０％。     

Microsatellite instability and loss of heterozygosity in oral squamous cell carcinoma in Malaysian population

Loss of heterozygosity (LOH) and microsatellite instability (MSI) have been documented as important events in oral squamous cell carcinoma (OSCC). Five microsatellite markers D3S192, D3S966, D3S647, D3S1228 and D3S659 were selected on chromosome 3p because of high frequency of alterations reported in head and neck squamous cell carcinoma and the involvement of von Hippel Lindau (VHL) at 3p25-26 and the fragile histidine triad (FHIT) at 3p14.2 genes proven in many tumour types. A total of 50 archival tissue samples of OSCC and corresponding normal samples were analyzed for LOH and MSI status. The overall LOH for the markers selected on 3p was 56 out of 189 informative cases (29.6%). The most frequent LOH was identified for the marker D3S966 which was 18/42 (42.8%) of informative cases suggesting the presence of putative tumour suppressor genes (TSGs) in this loci. In this study, high frequency of microsatellite instability was found in D3S966 which was 28.6% of informative cases; this reveals the possibility of mutations of MMR genes in this region. Frequent microsatellite alterations (MA) were observed in 3 markers D3S966 (71.4%), D3S1228 (56.7%) and D3S192 (41.0%). There was no significant association between LOH with gender, tumour stages and differentiation grades. However, there was a significant association between tumour stage and differentiation grades with MSI status in OSCC in Malaysian population with p values of 0.002 and 0.035, respectively. There was also a significant association between MA and differentiation grades (p=0.041).     

Detailed Deletion Mapping of Chromosome 9p21-22 in Nasopharyngeal Carcinoma

Previous studies have showed that Epstein-Barr virus (EBV) infection, certain environmental factors and genetic factors were found to be closely associated with nasopharyngeal carcinoma. The rates of NPC in southern China and southeast Asia are 25 times higher than that of in western countries. The statistic analysis revealed 5%-10% NPC patients have family history, there, genetic susceptibility might be an important factor in the pathogenesis of NPC. Unfortunately the alterations of com…     

Detailed deletion mapping of chromosome 9p21–22 in nasopharyngeal carcinoma

Objective: To further refine the extent of deletion on chromosome 9p21–22 in nasopharyngeal carcinoma (NPC) and provide evidence for discovering new tumor suppressor gene. Methods: Loss of heterozygosity (LOH) on chromosome 9p21–22 was analyzed in 25 paired blood and tumor samples by using 11 high-density microsatellite polymorphic markers. Results: 17 of 25 cases (68.0%) showed LOH at one or more loci. Higher frequencies of LOH were found at four loci: D9S161 (35.0%), D9S1678 (31.5%), D9S263 (33.3%) and D9S1853 (33.3%), where 6 cases had a contiguous stretch of allelic loss. Conclusion: The minimal common region of deletion might be defined between D9S161 and D9S1853 (estimated about 2.7 cM in extent) at 9p21.1, suggesting that inactivation of one or more tumor suppressor genes located in this region may be an important step in NPC. This work was supported by a grant from the National “863” Project of China (No. 102-10-01-05).     

Microsatellite instability during the immortalization and transformation of human breast epithelial cells in vitro

The objective of this study was to determine whether microsatellite instability (MSI) and loss of heterozygosity (LOH) are involved in the immortalization of human breast epithelial cells (HBECs) in vitro and in the early stages of their transformation by benzo[a]pyrene (BP) and 7,12-dimethylbenz[a]anthracene (DMBA). We performed a genome-wide analysis of a total of 466 microsatellite DNA polymorphism loci along the X chromosome and the 22 pairs of human autosomes. MSI was found in the immortalized MCF-10F cells at the following loci: D11S1392 (on chromosome 11p13) and D17S849 (at 17p13.3), D17S796 (at 17p13.1), D17S513 (at 17p13.1), TP53 (at 17p13.1), D17S786 (at 17p13.1), and D17S520 (at 17p12) on chromosome 17. The BP-transformed cells exhibited MSI in the same loci and also in locus D11S912 (at 11q25). The more transformed BP1E cells also exhibited MSI on chromosome 13q12-13 at D13S260 and D13S289, markers known to flank the breast cancer susceptibility gene BRCA2. In the DMBA-transformed D3 and D3-1 cells, MSI was observed at the locus D13S260 in addition to the previously reported locus D16S285 (at 16q12.1). No LOH was observed on any of the chromosomes tested in these cells. These observations led us to conclude that the immortalization and transformation of HBECs may involve defects in mechanisms responsible for the cell's genomic stability, such as DNA replication and DNA mismatch repair.     

Microsatellite alterations on chromosome 9 in chewing tobacco-induced oral squamous cell carcinomas from India

Genomic instability as reflected by microsatellite alterations in specific target regions is an important characteristic of oral squamous cell carcinoma (OSCC). Microsatellite instability (MSI) and loss of heterozygosity (LOH) on chromosome 9 has been reported as an early event in oral cancers, primarily from patients in the USA and UK. Hence, we examined 77 primary oral cancer tissues and corresponding peripheral blood cell (PBC) DNA from Indian oral cancer patients for LOH and MSI, using a panel of 11 microsatellite markers spanning chromosome 9 on p and q arms. The patients were long-time (minimum 10 years) tobacco chewers. The matched DNA samples were amplified by polymerase chain reaction, resolved on a denaturing polyacrylamide gel and visualized by silver staining. An overall of 62% (48/77 cases) of the patients demonstrated microsatellite alterations including 27% MSI and 52% LOH, although at individual loci MSI was observed in 3-8% patients and LOH in the informative cases ranged from 4 to 41%. A majority of the alterations occurred on the p arm at 9p21-23, with 85% (41/48 cases) genetic alterations concentrated between markers D9S157 and D9S161. Multiple alterations were seen in 56% (27/48) of the affected cases with 17 patients showing microsatellite alterations in three to eight loci. Our data show the incidence of genetic alterations primarily in the chromosomal region 9p21-23, and may be indicative of involvement of p16 (CDKN2) tumor suppressor gene on chromosome 9p21, in a subset of chewing tobacco-induced oral cancers.     

Prognostic implications of microsatellite genotypes in gastric carcinoma

Microsatellite alterations such as loss of heterozygosity (LOH) and microsatellite instability (MSI) are observed in most (70% to 80%) gastric carcinomas. To determine whether the microsatellite genotypes are correlated with clinicopathological features, 118 patients with gastric carcinomas were examined by using polymorphic microsatellite markers for LOH on 5 gastric cancer-associated chromosome arms and non-polymorphic BAT markers for MSI. Microsatellite genotypes were categorized as high-frequency MSI (MSI-H), high-level LOH (LOH-H), low-level LOH (LOH-L) and LOH non-detectable (LOH-N). A significant fraction of the MSI-H, LOH-H and LOH-L types was observed in intestinal-type gastric carcinomas, whereas the LOH-N type was highly associated with diffuse-type tumors (p = 0.00162). There was a close relationship between microsatellite genotype and TNM (tumor-node-metastasis) stage (p = 0. 001). Univariate analysis showed that patients of LOH-H or LOH-N types and those of MSI-H or LOH-L types correlated with poor and favorable survival, respectively, not only in all tumor stages (p = 0.0001) but also in stages II and III (p = 0.0271). It is likely that the major genotypes of gastric carcinomas can be placed into at least 4 microsatellite categories, thus allowing the construction of a comprehensive genetic classification useful for the prediction of diverse clinical courses.     

Assessment of the frequency of genetic alterations (LOH/MSI) in patients with intraepithelial cervical lesions with HPV infection: a pilot study

In the present study, we analyzed (1) the type of HPV infection and (2) the frequency of loss of heterozygosity and microsatellite imbalance (LOH/MSI) in normal cytology and cervical intraepithelial neoplasia (CIN1-3). The cytological material included: low-grade squamous intraepithelial lesions (CIN1, n = 11), high-grade lesions (CIN2 and CIN3, n = 13), and cytologically normal cells from non-neoplastic cervical samples (n = 8). HPV genotyping was done using RealLine HPV 16/18 kit. We used 20 microsatellite markers from: 1p31.2, 3p14.3, 3p21.3, 3p22.2, 3p24.2, 3p25.3, 7q32.2, 9p21.3, 11p15.5, 12q23.2, and 16q22.1. LOH/MSI was correlated with clinicopathological parameters. The presence of HPV DNA was revealed in 78.13 % samples, including normal cytology. LOH/MSI was the most frequent for: 3p25.3 (39 %), 3p22.2 (20.83 %), 3p24.2 (20 %), and 3p14.3 (16.67 %). It was demonstrated that D3S1234 (FHIT; 3p14.3), D3S1611 (MLH1; 3p22.2), D3S1583 (RARB; 3p24.2), D3S1317 and D3S3611 (VHL; 3p25.3) could differentiate patients with CIN2/CIN3 versus CIN1, showing significantly higher frequency in CIN2/CIN3. LOH/MSI frequency for other than 3p markers was lower, 10–22.2 %. The simultaneous occurrence of LOH/MSI for several markers (OFAL) was higher in CIN2/CIN3. Significant differences in OFAL were found between samples with versus without HPV infection. In HPV-positive patients, significant differences in OFAL were found between normal cytology, CIN1 and CIN2/CIN3. HPV infection influences the increase in LOH/MSI frequency, especially in tumor suppressor gene loci. Several studied microsatellite markers seem to be useful for CIN grading. Hopefully, the obtained results, if confirmed on larger patient cohort, would allow creating a panel of markers supporting clinical diagnosis in patients with HPV infection.     

Loss of heterozygosity on chromosome 10q is associated with earlier onset sporadic colorectal adenocarcinoma

Recent studies have shown that loss of heterozygosity (LOH) on chromosome 10q is a frequent event in a number of tumour types including colorectal cancers. Because previous studies have used markers located mainly distally on chromosome 10, we have examined 114 sporadic colorectal adenocarcinomas for LOH using a panel of 9 highly polymorphic microsatellite markers spanning the long arm of chromosome 10. Using microdissected tumour material, LOH of one or more chromosome 10q markers was a frequent event (75 of 114; 66%). The highest frequency of loss (42 of 96; 44%) was observed at the marker D10S1790 located at 10q21.1. The mean age of presentation, of patients with LOH of D10S1790 was significantly (p = 0.0006) lower (67.1 years) compared to patients with retention of this marker (73.5 years). When we compared frequency of loss at this marker in patients presenting before 70 years of age (68%) to those above 70 years (23%) we observed a significant difference (p < 0.0001). Statistical analysis between loss, or instability at other markers and clinicopathological features did not show any significant associations. In addition LOH at D10S1790 was infrequent in adenomas (2 of 20; 10%) compared to adenocarcinomas (42 of 96; 44%) (p = 0.0047), suggesting that loss within this region is a late event in colorectal tumorigenesis. The association of loss at D10S1790 and an earlier age of presentation in adenocarcinomas suggests that this locus may harbor a tumour suppressor gene(s), which affects the rate of colorectal tumour progression. Identification of this region of genetic loss further refines our understanding of the paradigm in this tumour type of multiple-steps responsible for initiation and progression.     

Loss of heterozygosity on chromosome 14 in primary nasopharyngeal carcinoma

Multiple genetic alterations are believed to be involved in the pathogenesis of nasopharyngeal carcinomas (NPC). Loss of heterozygosity (LOH) of chromosomes 3p, 9p and 11q were previously reported in NPC. In order to further define the genetic alterations in NPC, 42 pairs of normal and tumor DNA of NPC were examined for LOH on chromosomes 5p, 5q, 6q, 14q, 15q, 16p, 16q, 17q using 16 polymorphic microsatellite markers. Frequent LOH (33%; 7 out of 21 cases) was observed in chromosome 14q at locus D14s81 (14q31). In order to define the common region of deletion, nine polymorphic microsatellite markers on 14q were examined for LOH in NPC. A common region of deletion was defined in NPC at chromosome 14q24.3-q32.1 flanked by two microsatellite markers D14s76 and D14s45. The common region of deletion (14q24.3-32.1) identified in NPC overlapped with the deleted regions of 14q reported in several human cancers. In 2 cases of NPC, the pattern of LOH revealed the presence of another commonly deleted region defined by loci D14s63 and D14s69 (mapped to 14q11.1-24.1) and located proximal to locus D14s76(14q24.3). This study suggests that multiple tumor suppressor genes present on chromosome 14q are involved in the pathogenesis of NPC.     

乳腺导管原位癌与浸润性导管癌染色体微卫星杂合性缺失的比较

目的:研究乳腺导管原位癌与浸润性导管癌染色体3p区域微卫星杂合性缺失(loss of heterozygosity,LOH)的发生情况.方法:选取本院2005年9月至2009年2月手术切除石蜡包埋的乳腺癌组织切块43例,应用激光显微切割技术留取组织中乳腺浸润性导管癌(invasive ductal type carci...     

乳腺癌与癌前病变的微卫星不稳定性与3p杂合性缺失

目的探讨微卫星不稳定性(MSI)与3号染色体短臂杂合性缺失(LOH)在乳腺癌发生机制中的作用及其临床病理学意义。方法采用PCR-SSLP及银染方法检测41例乳腺癌和13例癌前病变中MSI状态以及3p上11个微卫星位点LOH发生情况;应用免疫组化SP法检测错配修复(MMR)基因hMLH1、hMSH2和3p上相关基因的表达情况。结果(1)乳腺癌MSI发生率为36.6%,低分化乳腺癌MSI发生率明显高于高中分化组;癌前病变的发生率为15.4%;良性增生均表现微卫星稳定。(2)乳腺癌中微卫星异常主要分布于D3S1766、D2S2739和TP53 3个位点,癌前病变和乳腺癌具有相同的高频不稳定位点D3S1766和D2S2739。(3)97.0%乳腺癌患者发生3p LOH,检出率较高的位点分别是D3S1295、D3S1029和D3S1038。癌前病变患者3p LOH发生率为41.7%,缺失率较高的位点是D3S1295和D3S1029。(4)hMLH1和hMSH2蛋白在乳腺癌中阳性表达率分别为45.0%和40.0%,在癌前病变中分别为61.5%和76.9%,均明显低于良性增生组(P<0.05)。乳腺癌中两种蛋白阳性率与组织学分级相关(P<0.05),高分化组明显高于低中分化组。MSI 乳腺癌和癌前病变均表现MMR蛋白表达缺失。结论错配修复基因表达缺陷和MSI是乳腺癌多步骤发展过程的早期事件,在进展阶段MSI与乳腺癌低分化相关;D3S1766和D2S2739可能是检测乳腺癌与癌前病变MSI较敏感的位点。3p最小共同缺失区位于3p14-p25,提示该区域有与乳腺肿瘤发生发展相关并影响其生物学行为的候选抑癌基因。     

High resolution mapping of chromosome 6 deletions in cervical cancer.

Chromosome 6 is frequently affected in different tumors. However, little information exists on chromosome 6 deletions in cervical cancer. We have studied loss of heterozygosity (LOH) and microsatellite instability (MIN) in 62 invasive squamous cell carcinomas of the cervix (CC) using 19 polymorphic microsatellite markers spanning both arms of chromosome 6 and one marker located at 5p15. We found that LOH at chromosome 6 is a common feature of cervical carcinomas: 90% (56/62) of CC had LOH at least at one locus and about 58% (36/62) had LOH on both arms of chromosome 6. The highest LOH incidence was shown in HLA region (6p21.3-6p21.1) with markers D6S273 and D6S276 in 52.7% and 45.2% of informative cases respectively. Frequent LOH on 6q was found at loci D6S311 (6q24-25. 1), D6S305 (6q26) and D6S281 (6q27-6qter) in 37.8%, 33.3% and 39.0% of informative cases respectively. There was no significant correlation observed between clinical parameters of cervical cancer (age, histologic grade, clinical stages and progression) and LOH frequency. Microsatellite instability was found in 3 out of 62 cases (4.8%) at three and more loci out of 20 tested. The study shows that several regions on 6p and 6q may harbour potential tumor-suppressor genes important for cervical cancer progression.     

精细定位和克隆9p21-22区域内鼻咽癌候选抑瘤基因

目的：进一步精细限定鼻咽癌９p２１－２２区域等位基因杂合性丢失的频率和范围,筛选 和克隆其共同缺失区内鼻咽癌相关的候选抑瘤基因。方法：应用１１个定位于９p２１－２ ２区域的高密度微卫星位点,检测２５例低分化鼻咽癌患者的杂合笥技失,确定其共同缺失区;用ＲＴ－ＰＣＲ和Ｎｏｒｔｈｅｒｎ筛出在鼻咽癌细胞株ＨＮＥ１和鼻咽癌活检组织中表达下调的、定位于共同缺失区内的３’末端ＥＳＴs（Ｅｘｐｒｉｓｓ Ｓｅｑｕｅｎｃ