荧光原位杂交技术检测肺腺癌p53基因缺失及其临床意义

[目的]探讨荧光原位杂交(FISH)技术在检测p53基因缺失中的应用,并评估其应用于肺腺癌诊断的可行性及临床应用前景。[方法]采用FISH技术在基因水平上检测30例肺腺癌及20例良性病变的p53基因缺失情况,比较两组间有无统计学差异,同时建立阳性检测的阈值,比较两组间p53基因缺失的阳性率。采用免疫组化检测30例肺腺癌p53蛋白表达情况,并分析肺腺癌p53基因缺失和p53蛋白阳性表达之间有无统计学意义。[结果]30例肺腺癌p53基因缺失率为(38.3%±8.9%),20例良性病变对照组为(13.3%±2.4%),两组间有显著统计学差异(P<0.01)。p53蛋白阳性组与阴性组间的p53基因缺失率无统计学意义(P>0.05)。[结论]p53基因缺失的高表达在肺腺癌的发生中可能起重要作用,用FISH技术检测p53基因缺失率可能对肺腺癌诊断和治疗提供更加准确的依据。     

大鼠肺鳞癌中p16^INK4A和p19^ARF基因的缺失研究

目的：研究p16^INK4a和p19^ARF基因的缺失与大鼠肺鳞癌发生发展的关系。方法：利用显微切割和聚合酶链反应(PCR)技术，在10例正常大鼠支气管黏膜上皮细胞、16例癌前病变细胞和34例肺鳞癌组织分别检测p16^INK4AE1α和p19^ARFE1β的缺失。结果：10例大鼠正常支气管黏膜上皮细胞均未发现有p16^INK4aE1α和p19^ARFE1β的缺失。在16例癌前病变中发现p16^INK4aE1α和p19^ARFE1β缺失的检出率分别为12．50％(2／16)和6．25％(1／16)；p16^INK4aE1α或(和)p19^ARFE1β总缺失率为18.75％(3／16)。34例大鼠肺鳞癌中p16^INK4aElα和p19^ARFE1β缺失的检出率分别为32．35％(11／34)和41．18％(14／34)，其中有9例两者同时缺失，p16^INK4aE1α或(和)p19^ARFE1β总缺失率为47．06％(16／34)。肺鳞癌的p19^ARF1β的缺失率显著高于癌前病变，P=0．012。结论：在诱发性大鼠肺鳞癌的发生发展中，p16^INK4a基因的缺失可能在早期已起作用，p19^ARF的生物学活性可能强于p16^INK4a。p16^INK4a和p19^ARF4a基因的同时缺失损伤了Rb和p532条肿瘤抑制途径，这可能有助于大鼠肺鳞癌的恶性进展。     

大鼠肺鳞癌中p16INK4a和p19ARF基因的缺失研究

目的研究p16INK4a和p19ARF基因的缺失与大鼠肺鳞癌发生发展的关系.方法利用显微切割和聚合酶链反应(PCR)技术,在10例正常大鼠支气管黏膜上皮细胞、16例癌前病变细胞和34例肺鳞癌组织分别检测p16INK4aE1α和p19ARFE1β的缺失.结果10例大鼠正常支气管黏膜上皮细胞均未发现有p16INK4aE1α和p19ARFE1β的缺失.在16例癌前病变中发现p16INK4aE1α和p19ARFE1β缺失的检出率分别为12.50%(2/16)和6.25%(1/16);p16INK4aE1α或(和)p19ARFE1β总缺失率为18.75%(3/16).34例大鼠肺鳞癌中p16INK4aE1α和p19ARFE1β缺失的检出率分别为32.35%(11/34)和41.18%(14/34),其中有9例两者同时缺失,p16INK4aE1α或(和)p19ARFE1β总缺失率为47.06%(16/34).肺鳞癌的p19ARFE1β的缺失率显著高于癌前病变,P=0.012.结论在诱发性大鼠肺鳞癌的发生发展中,p16INK4a基因的缺失可能在早期已起作用,p19ARF的生物学活性可能强于p16INK4a.p16INK4a和p19ARF基因的同时缺失损伤了Rb和p53 2条肿瘤抑制途径,这可能有助于大鼠肺鳞癌的恶性进展.     

PTPN13和FAK在肺鳞癌中的表达及其临床意义

目的:研究PTPN13和FAK在肺鳞癌中的表达及意义,为建立早期预防、早期诊断、预后预警及个体化治疗的肺鳞癌防治新策略奠定基础.方法:免疫组化法观察PTPN13及FAK在肺鳞癌及癌旁组织中的表达情况.结果:PTPN13表达与肺鳞癌的临床分期、组织分化程度及淋巴结转移呈显著负相关(P<0.05);FAK表达与肺鳞癌的临床分期、组织分化程度及淋巴结转移呈显著正相关(P<0.05);PTPN13和FAK在肺鳞癌组织中的表达呈显著负相关(P<0.05).结论:PTPN13基因是肺鳞癌发生相关的抑癌基因,其抑制肿瘤侵袭转移的生物学功能可能与FAK磷酸化有关.     

PTPN13和FAK在肺鳞癌中的表达及其临床意义

目的：研究PTPN13和FAK在肺鳞癌中的表达及意义,为建立早期预防、早期诊断、预后预警及个体化治疗的肺鳞癌防治新策略奠定基础。方法：免疫组化法观察PTPN13及FAK在肺鳞癌及癌旁组织中的表达情况。结果：PTPN13表达与肺鳞癌的临床分期、组织分化程度及淋巴结转移呈显著负相关（P〈0.05）;FAK表达与肺鳞癌的临床分期、组织分化程度及淋巴结转移呈显著正相关（P〈0.05）;PTPN13和FAK在肺鳞癌组织中的表达呈显著负相关（P〈0.05）。结论：PTPN13基因是肺鳞癌发生相关的抑癌基因,其抑制肿瘤侵袭转移的生物学功能可能与FAK磷酸化有关。     

应用M-FISH和CGH技术研究肺腺癌基因组变化

[目的]分析肺腺癌中染色体异常变化和基因改变，探讨肺腺癌细胞遗传物质的改变与肺腺癌发生发展之间的关系。[方法]应用M-FISH技术，检测3株肺腺癌细胞株的染色体数目及结构畸变情况．应用CCH技术对50例肺腺癌组织提取的全基因组DNA进行检测，以了解肺腺癌全基因组的变化。[结果]M-FISH结果显示肺腺癌细胞中存在许多复杂的染色体重排，5、6、11、12、17号染色体最频繁参与染色体间的易位。CGH发现，在50例肺腺癌标本基因组中，最常见的扩增区域是1q、2p、3q、5p、5q、7p、8q、11q、12q、14q、16p、17q、19q、20q、21q、22q。最常见的缺失区域是2q、3p、4p、5q、7q、8p、9p、13q、14q、17p。其中最常见的扩增位点是16p13，阳性率达50％，最常见的缺失位点是8p22，阳性率达38％。[结论]M-FISH和CGH技术是研究肺腺癌基因组变化的强有力工具，该实验中发现的基因可能代表了与肺腺癌的病理、诊断相关的候选基因。     

喉鳞癌9p13-23区域微卫星杂合性缺失精细作图及其临床意义

背景与目的:微卫星(microsatellite)是广泛分布于生物基因组中的DNA重复序列,与许多重要基因紧密连锁。在肿瘤中微卫星象抑癌基因一样常常发生杂合性缺失(lossofheterozygosity,LOH)。在某些特定肿瘤中有些微卫星位点存在高频发的LOH“热点”,而与该肿瘤发生、发展相关的抑癌基因很可能就隐藏在这些“热点”附近。微卫星LOH的研究是寻找新的抑癌基因的重要方法。本研究旨在探讨喉鳞癌9p13-23区域微卫星LOH的热点及其与喉鳞癌患者临床病理特征的关系。方法:采用显微切割法从喉鳞癌组织石蜡切片中挑取肿瘤组织,苯酚氯仿抽提肿瘤组织和外周血淋巴细胞基因组DNA,应用9p13-23区域13个多态性微卫星标记对42例喉鳞癌组织及其相应的外周血淋巴细胞DNA进行PCR扩增和变性凝胶电泳,并对频发微卫星LOH的发生与喉鳞癌患者临床病理特征的关系进行比较分析。结果:(1)42例喉鳞癌组织9p13-23区域微卫星LOH的发生率是97.6%(41/42),LOH发生率最高者是位于9p22-23的D9S162(89.5%),其次是位于9p21的D9S171(80.0%),与p16基因紧密连锁的D9S1748的LOH发生率仅50.0%;(2)等位基因缺失作图发现42例喉鳞癌组织在9p13-23上存在两个明显的LOH较小区域,分别位于9p21的D9S161～D9S171之间和9p22-23的IFNA～D9S162之间;(3)年龄<60岁、声门     

散发性结直肠癌患者5号染色体杂合缺失分析

目的：探讨散发性结直肠癌患者5号染色体上与抑癌基因相关的杂合缺失（LOH）情况,并探讨新的抑癌基因位点,方法：对83例散发性结直肠癌患者基因组DNA,以15个不同荧光标记的高度多态性微卫星引物（平均遗传距离12．67cm)扩增相应的微卫星位点,用ABI PRISM 377测序仪进行基因扫描,统计各位点杂合缺失率。结果：在15个微卫星位点中,平均杂合缺失率为25．80％,5p中最高为D5S416,占48．15％,5q中最高为D5S471,占38．71％,D5S471周围的3个位点（D5S428,D5S2027 和 D5S2115）也存在高频的杂合缺失（＞30．00％）,结论：5号染色体上存在着高频的杂合缺失,其中5q13.3-31.1区域中,有与结直肠癌发生密切相关的APC,MCC,CTNNA1及IL家族等基因,而在5p15.1上的D5S416的杂合缺失率高达48．15％,此区域至今尚未发现与结直肠癌相关的基因位点,估计可能有未知的抑癌基因存在。     

EGFR突变的肺腺癌患者中Rb和磷酸化Rb的表达及临床特征分析

背景与目的 Rb作为重要的抑癌基因,调控细胞周期的进程.各种原因导致的Rb功能异常均可导致细胞的持续过度增殖从而导致肿瘤的发生.Rb蛋白表达缺失或减弱及过度磷酸化是Rb功能异常的重要机制.具有突变的表皮生长因子受体(epidermal growth factor receptor,EGFR)基因是肺腺癌重要的驱动基因,在肺癌的发生发展中起着重要的作用.本研究目的在于探讨Rb在EGFR突变的肺腺癌中的存在状态.方法 取23例具有EGFR突变的肺腺癌标本,用免疫组化的方法分析Rb、pRb-780、pRb-795表达状态及临床特征.结果在23例EGFR突变的肺腺癌患者中Rb蛋白表达缺失/减弱频率为69.6%,pRb-780、pRb-795过表达的频率分别为73.9%、69.6%.23例患者均存在Rb表达缺失/减弱或Rb过度磷酸化.进一步分析发现,pRb-780过表达在晚期患者中发生更多(P=0.022);pRb-795过表达在晚期患者中发生更多,但无统计学差异(P=0.074).结论 在EGFR突变的肺腺癌患者中,频繁发生Rb的表达缺失/减弱或过度磷酸化,Rb功能异常是EGFR突变肺腺癌患者重要的发病机制.     

环氧化酶-2及p53在非小细胞肺癌中的表达与临床意义

研究表明肺癌发生、发展是多种癌基因和抑癌基因相互作用的结果。目前认为环氧合酶-2（COX-2）参与肺癌的发生、发展、转移等多方面。p53基因是最重要的抑癌基因之一，p53缺失突变与肺癌的发生、发展有关。p53突变与COX-2在非小细胞肺癌（NSCLC）的发生、发展中可能具有协同作用。     

Loss of heterozygosity at loci of candidate tumor suppressor genes in microdissected primary non-small cell lung cancer

To investigate the etiological association of allelic loss at chromosomal regions containing tumor suppressor genes (TSGs) in non-small cell lung cancer (NSCLC) in Taiwan, we examined 48 microdissected NSCLC samples for loss of heterozygosity (LOH) at nine loci where TSGs are localized nearby. The associations of LOH at each locus with clinicoparameters and prognosis were also examined. The frequent LOH was observed using markers, D3S1285 near the FHIT gene (58.3%), D17S938 near the p53 gene (56.7%), D9S925 near the p16 gene (54.5%), and D13S153 near the RB gene (47.6%). The occurrence of LOH at each TSG locus was compared with the patients' clinicoparameters. The incidence of LOH at D17S938 (p53 gene) and D3S4545 (VHL gene) was significantly higher in squamous carcinoma tumors than in adenocarcinoma tumors (P = 0.003 and 0.024, respectively). LOH of these two loci also occurred frequently in tumors from smoker patients compared to that from nonsmoker patients (P = 0.013 and 0.025, respectively). LOH at D13S153 (RB gene) was also associated with smoking (P = 0.008). In addition, the prognostic analyses indicated that the patients with LOH at D18S535 (18q21, near the SMAD2/4 gene) had significantly longer post-operative survival time compared to those without LOH (P = 0.03). Our results suggested that LOH at FHIT, p53, and p16 genes may occur frequently in NSCLC patients in Taiwan. In addition, LOH at p53, RB, and VHL may associate with smoking or squamous carcinoma patients and LOH at SMAD2/4 may be correlated with better prognosis.     

Genome-wide allelotyping of lung cancer identifies new regions of allelic loss, differences between small cell lung cancer and non-small cell lung cancer, and loci clustering

To identify the major tumor suppressor gene (TSG) loci involved in the pathogenesis of lung cancer, we have conducted a high-resolution (10 cM), genome-wide search of loss of heterozygosity (LOH). Thirty-six lung cancer cell lines [14 small cell lung cancers (SCLCs) and 22 non-SCLCs (NSCLCs)] and their matched control DNAs were analyzed using 399 fluorescent microsatellite markers from the ABI Prism linkage mapping set v.2 on an ABI 377 sequencer/genotyper. Overall, 22 different regions with more than 60% LOH were identified: (a) 13 regions with a preference for SCLC; (b) 7 regions with a preference for NSCLC; and (c) 2 regions affecting both SCLC and NSCLC. The chromosomal arms with the most frequent LOH were 1p, 3p, 4p, 4q, 5q, 8p, 9p (p16), 9q, 10p, 10q, 13q (Rb), 15q, 17p (p53), 18q, 19p, Xp, Xq. In addition, new homozygous deletions were found at 2p23, 8q24, 18q11, and Xq22. On average, 34% (SCLC) to 36% (NSCLC) of markers showed allele loss in individual tumors, with an average size of subchromosomal region of loss of five to six markers (50-60 cM). Whereas SCLC and NSCLC had different regions of frequent LOH (hot spots), and NSCLC had more of these regions (n = 22) than SCLC (n = 17), in all other parameters (fractional allelic loss, number of breakpoints, and number of microsatellite alterations), SCLC and NSCLC were not significantly different. Clustering analysis revealed correlations between LOH on different chromosomes that suggest previously unknown genetic interactions for lung cancer development. We conclude that (a) in lung cancer cell lines, at least 17-22 chromosomal regions with frequent allele loss are involved, suggesting that the same number of putative TSGs are inactivated; (b) SCLC and NSCLC frequently undergo different specific genetic alterations; and (c) clusters of TSGs are likely to be inactivated together. Overall, these data provide global estimates of the extent of genetic changes leading to lung cancer and will be useful for the positional cloning of new TSGs and for the identification of multiple new biomarkers for translational research.     

High-throughput loss-of-heterozygosity study of chromosome 3p in lung cancer using single-nucleotide polymorphism markers

Loss of DNA copy number at the short arm of chromosome 3 is one of the most common genetic changes in human lung cancer, suggesting the existence of one or more tumor suppressor genes (TSG) at 3p. To identify most frequently deleted regions and candidate TSGs within these regions, a recently developed single-nucleotide polymorphism (SNP)-mass spectrometry-genotyping (SMSG) technology was applied to investigate the loss of heterozygosity (LOH) in 30 primary non-small-cell lung cancers. A total of 386 SNP markers that spanned a region of 70 Mb at 3p, from 3pter to 3p14.1, were selected for LOH analysis. The average intermarker distance in the present study is approximately 180 kb. Several frequently deleted regions, including 3p26.3, 3p25.3, 3p24.1, 3p23, and 3p21.1, were found. Several candidate TSGs within these frequently detected LOH regions have been found, including APG7L at 3p25.3, CLASP2 at 3p23, and CACNA2D3 at 3p21.1. This study also showed that SMSG technology is a very useful approach to rapidly define the minimal deleted region and to identify target TSGs in a given cancer.     

Loss of heterozygosity of the Mutated in Colorectal Cancer gene is not associated with promoter methylation in non-small cell lung cancer

'Mutated in Colorectal Cancer' (MCC) is emerging as a multifunctional protein that affects several cellular processes and pathways. Although the MCC gene is rarely mutated in colorectal cancer, it is frequently silenced through promoter methylation. Previous studies have reported loss of heterozygosity (LOH) of the closely linked MCC and APC loci in both colorectal and lung cancers. APC promoter methylation is a marker of poor survival in non-small cell lung cancer (NSCLC). However, MCC methylation has not been previously studied in lung cancer. Therefore, we wanted to determine if MCC is silenced through promoter methylation in lung cancer and whether this methylation is associated with LOH of the MCC locus or methylation of the APC gene. Three polymorphic markers for the APC/MCC locus were analysed for LOH in 64 NSCLC specimens and matching normal tissues. Promoter methylation of both genes was determined using methylation specific PCR in primary tumours. LOH of the three markers was found in 41-49% of the specimens. LOH within the MCC locus was less common in adenocarcinoma (ADC) (29%) than in squamous cell carcinoma (SCC) (72%; P=0.006) or large cell carcinoma (LCC) (75%; P=0.014). However, this LOH was not accompanied by MCC promoter methylation, which was found in only two cancers (3%). In contrast, 39% of the specimens showed APC methylation, which was more common in ADC (58%) than in SCC (13%). Western blotting revealed that MCC was expressed in a subset of lung tissue specimens but there was marked variation between patients rather than between cancer and matching non-cancer tissue specimens. In conclusion, we have shown that promoter methylation of the APC gene does not extend to the neighbouring MCC gene in lung cancer, but LOH is found at both loci. The variable levels of MCC expression were not associated with promoter methylation and may be regulated through other cellular mechanisms.     

Hypermethylation of the tumor suppressor gene RASSFIA and frequent concomitant loss of heterozygosity at 3p21 in cervical cancers

Loss of heterozygosity (LOH) at chromosome 3p21 is frequent in cervical cancers. The candidate tumor suppressor gene, RASSF1A located at 3p21.3, is found to be inactivated in several major human cancers, implicating its significance in carcinogenesis. We aimed to investigate the status of RASSF1A in cervical cancers. The mutation and methylation status of RASSF1A were analysed in 4 cervical cancer cell lines, 50 primary cervical cancers including 33 squamous cell carcinoma (SCC), 17 adenocarcinoma (AC) and 11 normal controls. The primary cancer samples were also detected for LOH at 3p21 and human papillomavirus (HPV). Hypermethylation of RASSF1A was detected in 30% of SCC, 12% of AC and in 1 of the 4 cancer cell lines but was absent in all normal cases. Methylation of the cancer cell line was associated with loss of gene expression, which was restored by demethylation. About 67% (8 of 12) of hypermethylated primary cancers showed concomitant LOH at 3p21. No somatic mutation was found in all primary cancer samples or cell lines but 2 cases showed germline polymorphism at codon 133. Oncogenic HPV DNAs were found in most cancer samples. No correlation was detected between RASSF1A-hypermethylation or LOH at 3p21 and age of patient, HPV genotype, tumor grade and stage. Hypermethylation of RASSF1A occurs in a subset of cervical cancers, among which concomitant LOH at 3p21 is common. The results supported that RASSF1A may be one of the cervical cancer-related tumor suppressor genes located at 3p21 regions.     

Minimal deletion regions in lung squamous cell carcinoma: association with abnormality of the DNA double-strand break repair genes and their applications on gene identification and prognostic biomarkers

BACKGROUND: Lung squamous cell carcinoma (SCC) cells frequently exhibit markers of chromosome instability such as high fractional allelic loss (FAL). We postulated that alterations in the p53 damage responsive gene and in the double-strand break (DSB) repair genes, BRCA1 and XRCC5, are involved in patients with high FAL. In addition, chromosomal deletion analysis enables the delineation of the likely locations of tumor suppressor genes (TSG) and could provide molecular markers for disease classification. PATIENTS AND METHODS: To define the minimal deletion regions (MDRs), we used 92 microsatellites spanning 29 regions identified in our previous genome-wide chromosomal deletion study in 36 lung SCC patients to verify the maximal contiguous deletion loci. RESULTS: Eight MDRs at 2q35, 3p14.1-3p14.3, 3p22.2-p23, 3p25.3-3p26.3, 5q35.1-q35.2, 9p23-p24.1, 13q14.11-q14.2, and 17p13.1-p13.2 were found in lung SCC. The candidate genes GAS7 and OVCA2 in the MDR17pA (17p13.1-p13.2) were further examined for mRNA expression. Low expression of the GAS7 gene in 57% of patients analyzed suggested its importance in lung SCC tumorigenesis. In addition, we found a panel of five microsatellites (D3S1766, D4S2397, D4S2361, D13S175, and D17S974), which can be used as prognostic biomarkers in lung SCC. Furthermore, alteration in more than two genes in DSB repair-related pathways was more apparent in high FAL patients. CONCLUSIONS: Our results provide biomarkers that may be used for monitoring tumor progression and for positional cloning of new TSGs. Importantly, our data show direct evidence that alterations in DSB repair-related pathways are involved in the genomic instability verified by intensive microsatellites of lung SCC.     

Allelic loss on the short arm of chromosome 8 in oral squamous cell carcinoma.

Allelic deletions on the short arm of chromosome 8 (8p) are frequent events in many different types of malignant tumors, including head and neck tumors and oropharyngeal cancers. These regions are thought to harbor tumor suppressor genes. However, there has been no detailed analysis of loss of heterozygosity (LOH) on the chromosome arm 8p in oral squamous cell carcinoma (SCC). In order to estimate details of 8p loci involved in oral SCC, 32 patients with oral SCCs were examined for the LOH state 8p by PCR-LOH assay using 14 microsatellite markers. Based on our results a detailed deletion map of 8p showed LOH in at least one of the loci tested in 62.5% (20 of 32) of patients; and microsatellite instability (MI) was observed in 50% (16 of 32). The frequent LOH on this chromosome arm was identified at D8S87 and D8S258, mapped on 8p12 and 8p22, respectively. Fisher's exact test revealed no significant statistical correlation between the incidence of LOH or MI and clinicopathological features. Our observations indicate that the short arm of chromosome 8 may play a role in the pathogenesis of oral SCC; and that the two loci identified in this study may be tumor suppressor gene loci on 8p.     

16号染色体短臂散发性结直肠癌相关基因的精细定位

目的对散发性结直肠癌16号染色体短臂杂合缺失区间(LOH)进行精细定位,以期发现新的肿瘤相关基因.方法用覆盖16号染色体短臂的5个微卫星标记对83例散发性结直肠癌进行杂合缺失分析,初步定位候选区域后再用另5个微卫星标记对这一区域进行精细定位.PCR扩增相应位点的基因组DNA,并用ABI 377自动测序仪进行电泳.用Genescan 3.7 和Genotype 3.7软件进行遗传位点扫描及杂合缺失分析.杂合缺失与临床病理参数的关系比较采用χ2检验.结果 16号染色体短臂的平均杂合缺失率为24.58%,仅有一高频缺失位点D16S404,杂合缺失率达52.73%.对其精细定位后发现,最小杂合缺失区间应位于D16S406和D16S3126之间,约1.1 cM.而这一区间的杂合缺失与Dukes分期、肿瘤分化及淋巴结转移等无关.结论通过散发性结直肠癌16号染色体短臂杂合缺失的精细定位研究,发现了D16S406～D16S3126之间精度达1.1 cM的肿瘤相关基因候选区域.在这一区间内可能的肿瘤抑制基因为USP7基因,相邻的候选肿瘤抑制基因有EMP2.对这2个基因的深入研究可能明确新的散发性结直肠癌相关基因.     

Distinct regions of frequent loss of heterozygosity of chromosome 5p and 5q in human esophageal cancer

Loss of heterozygosity (LOH) studies reported thus far suggest that tumor suppressor loci on chromosome 5q are important in esophageal cancer (EC) while little is known about the involvement of chromosome 5p. To investigate the potential existence of tumor suppressor gene(s) on chromosome 5 contributing to the development of EC, we performed LOH studies using a total of 24 polymorphic markers spanning the entire chromosome 5. Seventy primary esophageal cancers were microdissected and allelic deletions were detected by polymerase chain reaction (PCR)-single strand conformation polymorphism or by microsatellite analysis. LOH was observed in at least 1 of the loci in 47 of 70 (67%) esophageal tumors. Initially, 40 tumors [24 squamous cell carcinomas (SCC) and 16 adenocarcinomas (ADC)], each with matched histologically normal esophageal mucosa, were analyzed at 15 marker loci on 5p and 5q. A novel locus, D5S667 on 5p15.2, exhibited the highest frequency of LOH (44%) in these tumors along with another previously reported region of frequent deletion, irf-1 (5q31.1). In a series of 30 additional EC tumors (11 SCC and 19 ADC), a detailed LOH analysis of chromosome 5p15.2 region was conducted using 10 additional polymorphic markers, which mapped the frequently deleted region within 1 cM. Overall, LOH at the D5S667 locus was observed more frequently in SCC than in ADC (62% vs. 23%, p = 0.01). This significant rate of LOH of a distinct region of chromosome 5p implicates the existence of a putative tumor suppressor gene locus involved in EC. Int. J. Cancer 78:600–605, 1998. © 1998 Wiley-Liss, Inc.