喉癌中13号染色体杂合性丢失研究

目的　为初步限定喉癌中 13号染色体抑癌基因的缺失区域和为发现及定位抑癌基因提供线索和依据。方法　应用聚合酶链反应 ( PCR) ,筛查了 58例喉癌 (包括 3例原位癌 )组织中染色体13q上 D13S765( 13q13) ,RB1.2 0 ( 13q14.2 ) ,D13S133( 13q14.3) ,D13S318( 13q2 1) 4个座位微卫星多态标记的杂合性丢失。结果　 3例原位癌中无一例发生 13q的杂合性丢失 ,55例浸润癌中在 13q一个以上座位出现杂合性丢失的频率为 4 5% ( 2 4 / 53) ,D13S765座位的杂合性丢失的频率最高 ,为 52 %( 2 2 / 4 2 )。结论　喉癌组织中染色体 13q缺失区域在 D13S765( 13q13)座位附近 ,RB1的近端 ,即在D13S765座位附近存在着与喉癌发生发展密切相关的抑癌基因 ,可能包括 RB1基因 ,它的失活与浸润期喉癌发生发展密切相关。     

Frequent loss of heterozygosity of the long arm of chromosome 7 is closely associated with progression of human gastric carcinomas

Loss of heterozygosity (LOH) on the long arm of chromosome 7 was examined using 5 polymorphic marker probes on 98 gastric carcinomas to elucidate a novel locus for development and progression of the tumors. Twenty-six (32%) of 82 informative cases showed LOH on 7q on at least one locus of 5 loci. Among 5 loci, LOH at D7S95 locus was most frequent, the incidence being 53% in well-differentiated gastric carcinomas and 33% in poorly differentiated and scirrhous gastric carcinomas respectively. At 3 loci, c-met, D7S63 and D7S22, the incidence of LOH was about 30% and 10% in well-differentiated and poorly differentiated gastric carcinoma cases respectively. In contrast, LOH at D7S64 was not detected in any gastric-carcinoma cases. Deletion mapping of 7q revealed that D7S95 locus was the essential region of LOH. Eight (62%) of 13 cases with LOH at D7S95 locus belonged to the most advanced stage grouping. Furthermore, 6 (75%) of 8 cases with abdominal dissemination showed LOH at D7S95. Therefore, cases with LOH at D7S95 showed significantly worse prognosis than the cases without the LOH in the stage-III and stage-IV groups. These findings overall suggest that D7S95 locus on 7q may contain a candidate suppressor gene for the progression of gastric carcinoma.     

Limiting the location of a putative human prostate cancer tumor suppressor gene at chromosome 13q14.3

We studied loss of heterozygosity (LOH) on human chromosome 13q in prostate cancer specimens to determine the location of a putative tumor suppressor gene (TSG) and to correlate these losses with the clinicopathological stage of the disease. Overall 13 (21%) of 61 specimens analysed had an allele loss on the long arm of chromosome 13. The most frequent (37%) LOH among the informative cases with allele losses was detected at the D13S284 locus on chromosome 13q14. 3. A portion of the DNA segment that spans this locus and is flanked by the microsatellite loci D13S153 and D13S163 was lost in 85% of the specimens with allele losses and was designated as a LOH cluster region (LCR). The LCR spans more than 6 Mbp of DNA. The results suggest that a TSG relevant for the development of prostate cancer is located telomeric to the RB locus. There was a significant correlation (P=0.0024) between chromosome 13q LOH and advanced metastatic disease, suggesting that loss of 13q14.3 region is associated with prostate cancer progression. However, further research must be conducted to establish the identity and function of this putative TSG.     

胶质母细胞瘤6号染色体杂合性丢失的初步研究

目的：寻找胶质母细胞瘤（GBM）6号染色体上可能存在肿瘤抑制基因的杂合性丢失（LOH）区域,为发现和定位肿瘤抑制基因（TSG）提供线索和依据。方法：应用聚合酶链反应（PCR）方法,采用荧光标记的引物及377型DNA序列自动分析仪,分析了21例GBM患者6号染色体上20个微卫星多态性标记的LOH。结果：6号染色体总的LOH检出率为47．6％（10／21）,在28．1％（81／288）能提价信息位上检测了LOH。其中,6p和6q的LOH检出率分别是28．6％（6／21）、38．1％（8／21）,在6q^tel上距短臂端粒201．1cM的微卫星位点D6S281检测到较高的LOH率（50％）,6q^16.3上D6S287的LOH率也高达50％,另外,6p^21.1-21.3上D6S276的LOH率也较高（35．3％）。结论：6号染色体分子遗传学异常改变可能在GBM的发生发展中起着重要作用,染色体6q^tel上的D6S281位点,6q^16.3上的D6S287和6p^21.1-21.3的D62S276位点所在的染色体区域可能存在与GBM相关的肿瘤抑制基因。     

Mutational and LOH analyses of the chromosome 4q region in esophageal adenocarcinoma

OBJECTIVE: Mortality due to esophageal adenocarcinoma has risen markedly, but the molecular mechanisms underlying this carcinogenesis are still incompletely understood. Findings from loss of heterozygosity (LOH) studies have suggested that the long arm of chromosome 4 might harbor tumor suppressor genes relevant to esophageal adenocarcinoma. METHODS: We performed LOH analysis of 4q in esophageal adenocarcinomas. Regions of LOH were further evaluated by studying two candidate tumor suppressor genes, hCDC4 and CARF, located within them. RESULTS: 54% of the adenocarcinomas examined showed allelic deletion. LOH was observed in 53, 40, 32, 38, and 27% of tumors at positions D4S1554 (the locus of CARF), D4S1572, D4S1548, D4S2934, and D4S3021, respectively. An area of allelic deletion (spanning 3 million bases) was identified at 4q31.1-3 in 37% of tumors. This region harbors a candidate tumor suppressor gene: hCDC4. However, sequencing of the coding regions of CARF and hCDC4 at 4q35 and 4q31, respectively, did not identify mutations. CONCLUSIONS: Our findings demonstrate frequent LOH in esophageal adenocarcinoma at several loci including a novel area of allelic deletion at 4q31.1-3. The results imply that mutational or other alterations at these loci may be involved in the pathogenesis of esophageal adenocarcinoma. Candidate tumor suppressor genes located within these regions merit further study.     

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.     

Deletion mapping of chromosome 4q in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) frequently shows a loss of heterozygosity (LOH) on chromosome 4q. In order to define the commonly affected region on chromosome 4q for further positional cloning of the putative tumor suppressor gene, we carried out allelic imbalance (AI) studies in 41 HCCs using a panel of 43 microsatellite markers. Thirty-four cases (82.9%) showed AI at one or more loci. Detailed deletion mapping identified 7 independent, frequently deleted regions on this chromosome arm. These were the (1) D4S1615 locus, (2) D4S1598 locus, (3) D4S620 locus, (4) D4S1566 and D4S2979 loci, (5) D4S1617 and D4S1545 loci, (6)D4S1537 locus; and (7) from the D4S2920 to D4S2954 locus. Among these 7 frequently deleted regions, 5 were associated with tumor differentiation. Our results suggest that several putative tumor suppressor genes may be present on chromosome 4q and that the AI of chromosome 4q may play a role in the aggressive progression of HCC. Int. J. Cancer (Pred. Oncol.) 79:356–360, 1998. © 1998 Wiley-Liss, Inc.     

Loss of two new loci on chromosome 8 (8p23 and 8q12-13) in human prostate cancer

Inactivation of tumor suppressor genes due to allelic loss is thought to be an important mechanism of gene alterations in prostatic carcinogenesis. Loss of sequences on the short arm of chromosome 8 (8p) has been reported in human cancers, especially of 8p22 and 8p12-21 in prostate cancer. By using PCR analysis of polymorphic microsatellite repeat markers at four 8p loci and three 8q loci in 60 tumors, we observed deletion of sequences at two other deletion domains (8p23, and 8q12-13). There was loss in 51 of 60 cases (85%) with at least one marker. Four distinct regions of loss detected were: i) at 8p23, at locus D8S262; ii) at 8p22, on locus D8S259; iii) at 8p12, on loci D8S255 and D8S285; iv) at 8q12-13, on loci between D8S260 and D8S528. We found that 29% of the tumors showed LOH at 8p23; 19% LOH on 8p22; 54% had LOH at 8p12; and 48% had LOH at 8q12-13. There was higher frequency of LOH at 3 or more loci in samples of T3 stage (62%) as compared to T2 stage (13.3%) which suggests higher incidence of LOH in advanced stage of prostate cancer. We report deletion of two novel loci at 8p23 and 8q12-13, these regions may contain putative tumor suppressor genes in prostate cancer.     

Commonly deleted region on the long arm of chromosome 7 in differentiated adenocarcinoma of the stomach.

Loss of heterozygosity (LOH) at several chromosomal loci is a common event in human malignancies. Frequent LOH on the long arm of chromosome 7 has been reported in various human malignancies, and investigators have identified the most common site of LOH as 7q31.1. We have identified ten chromosomal loci, including chromosome 7q, that have been shown by previous allelotype study to be sites of frequent LOH in differentiated adenocarcinoma of the stomach. In the present study, we performed a polymerase chain reaction (PCR) microsatellite analysis to define the common deleted region on 7q, using 14 polymorphic microsatellite markers in matched tumour and non-tumour DNAs from 53 patients with primary gastric carcinoma of the differentiated type. LOH at any locus on 7q occurred in 34% (18 out of 53) of the tumours. Although many tumours exhibited total or large interstitial deletions, we determined the smallest common deleted region to be at D7S480 (7q31.1). This is identical to the region identified for other human malignancies. These observations indicate that a putative tumour suppressor gene at 7q31.1 may be involved in the pathogenesis of differentiated adenocarcinoma of the stomach.     

Lack of correlation between survival and allele loss on chromosome 7q31–32 in primary breast cancer

High incidence of loss of heterozygosity (LOH), affecting the 7q31–32 chromosome region in sporadic primary human breast carcinomas suggests the presence of a tumor suppressor gene in this region which seems relevant to the development of breast cancer. To further determine the possible role of this region in the pathogenesis of human primary breast cancer and association with survival, LOH analysis was performed on 52 primary breast cancer patients using a set of highly polymorphic microsatellite markers. Our panel contained twenty biopsy cases of unknown survival, nineteen cases with more than five years survival and fourteen cases with less than two years survival. Corresponding normal and tumor DNAs were analyzed by polymerase chain reaction (PCR). The data presented here demonstrate that all patients were informative at least at one locus and 20 (38%) out of 53 cases showed LOH at one or more loci on chromosome 7q31–32. Relatively high incidence of LOH (34%) was detected at the D7S522 microsatellite marker located near to the cMet proto-oncogene while lower frequencies were observed at D7S523 (19%) and D7S495 (17%) loci, supporting the existence of a putative tumor suppressor gene at the chromosome 7q31.1 region. Our results suggest that allelic imbalance on 7q may occur at an early stage of breast carcinogenesis, as no correlation was observed between allelic loss and clinico-pathological data. This work was supported by Hungarian Research Grants ETT (T-019307) and OMFB (04-1-99-94-0328) given to Edith Olah.     

Loss of heterozygosity on chromosome 10q23 and mutation of the phosphatase and tensin homolog deleted from chromosome 10 tumor suppressor gene in Korean hepatocellular carcinoma patients

Loss of heterozygosity (LOH) in the 10q23 chromosomal region was analyzed in 18 tissue samples from Korean hepatocellular carcinoma (HCC) patients. LOH at the phosphatase and tensin homolog deleted from chromosome 10 (PTEN) region (D10S215, AFMa086wg9 and D10S541) was found in 8 of the 18 (44.4%) HCCs. LOH (20%) and microsatellite instability (26.7%) were also frequently found at the D10S2177 locus, which is located on the telomere side of the PTEN region. LOH was found in other loci, such as AFM280we1 and D10S2281. The presence of LOH in regions other than the PTEN region on chromosome 10q23 suggested the presence of additional tumor suppressor gene(s). PTEN mutation was found in only a subset of HCCs: A single base insertion at the end of the 5'-end splice signal (AG-GUAAGUU) in intron 5 and a silent mutation in exon 6 (codon 188, CTG-Val to CTA). Our data collectively suggest that the genetic alterations of chromosome 10q23, including the PTEN gene, could be important in hepatocarcinogenesis in the Korean population.     

原发性肝癌8号和16号染色体杂合子丢失的研究

目的:分析人肝细胞肝癌(HCC)组织中染色体8和16部分染色体片段的杂合子丢失及与临床病理关系,初步筛选HCC相关的抑癌基因,为HCC的早期诊断、预后预警提供可能的新分子标记物.方法:应用聚合酶链反应-变性聚丙烯酰胺凝胶-银染法分析45例HCC组织标本中分别位于染色体8和16上的具有高度多态性微卫星位点的杂合性丢失(LOH)状态.结果:发生LOH的总频率为68.89％ (31/45),其中D16S511位点的LOH发生率最高为53.33％ (24/45),其次是D8S261( 39.02％,16/41)和D8S499(34.88％,15/43).结论:染色体16q23、8p22-21.3及8p12区域的LOH发生频率高,可能存在与HCC发生发展相关的新的抑癌基因,特定位点的遗传变异可能与HBV感染、临床病理恶性程度等预后因素相关.     

Allelic loss on chromosome 17 in human ovarian cancer

In order to identify a common region of deletion on chromosome 17 potentially containing a tumor-suppressor gene, 27 ovarian carcinomas and 3 ovarian tumors of low malignant potential (LMP) were examined for loss of heterozygosity (LOH) at 6 p arm and 10 q arm loci. Ninety percent of all tumors had deletions at one or more loci. On the p arm, there was a single near-common region of deletion on 17p 13.3 (D/7S30/ pYNZ22.1; 86% LOH), an intervening locus with a low LOH rate, and a more proximal locus on 17p11.2 (D/7S58/pEW301; 82% LOH) with a high LOH rate. In less aggressive tumors, LOH at Df 7S30 was not accompanied by LOH at p53. The q arm had a common region of deletion for high-stage carcinoma at D/7S579 (Mfd 188; 74% LOH) on q21, a locus tightly linked to the familial breast-ovarian-cancer syndrome (BRCAI) locus. D/7S579 was lost in all informative high-stage carcinomas and retained in all low-stage carcinomas and tumors of LMP. There may be at least 2 tumor-suppressor genes, an early-acting gene on the p arm and a gene on the q arm involved in tumor progression and metastasis.     

Loss of heterozygosity and microsatellite instability in larynx cancer

We have examined 48 squamous cell cancers of the larynx for loss of heterozygosity (LOH) and microsatellite instability at chromosome 9p near the p16 tumour suppressor locus, at chromosome 17p at the p53 tumour suppressor locus, and at 17p at another microsatellite locus (D17S520). In p53 LOH was higher (33-45%) than in D17S520 (21%). Near the p16 locus LOH varied from 28-38%. Replication errors were found from at least one locus in 23% of the patients. These data suggest that p53 is an important gene in laryngeal cancer while loci around p16 appear less likely candidates.     

Identification of distinct regions of allelic loss on chromosome 13q in nasopharyngeal cancer from paraffin embedded tissues.

Our main purpose was to identify tumor suppressor gene loci on chromosome 13 responsible for nasopharyngeal cancer (NPC) development by analyzing loss of heterozygosity (LOH) and RB protein expression in paraffin embedded tissues. Normal and tumor DNA were extracted from microdissected samples, and their whole genomes were amplified using degenerate oligonucleotide primers. The polymerase chain reaction (PCR) products were analyzed by repeated amplification using primers derived from 16 microsatellite regions spanning the long arm of this chromosome. Among 50 informative cases, LOH was observed in 44 tumors. Thirty-one tumors displayed partial loss and provided an informative basis for detailed deletion mapping. Three minimal regions of loss were delineated; the first flanked by D13S120 and D13S219, the second by D13S126 and D13S119, and the third by D13S137 and 13qter. These 3 regions were linked to BRCA2 on 13q12, RB1 on 13q14, and 13q14.3-ter, respectively. Seven and 4 cases showed LOH either on 13q12 or 13q14, respectively. Nineteen cases showed LOH of both loci separately. One NPC displayed 13q12 and 13q14.3-ter LOH. RB protein expression was detectable in 76% of the cases. Ten out of 15 cases with the allelic losses limited to 13q14 showed RB protein expression. Contrasting that, 6 out of 7 cases devoid of RB protein expressions showed 13q14LOH. In conclusion, 13qLOH, involving 3 tumor suppressor gene loci, appears to be a frequent genetic event occurring during NPC development. However, other tumor suppressor genes besides RB1, may be responsible for the majority of 13q14LOH.     

A novel region of deletion on 13q33-q34 in esophageal squamous cell carcinoma

Chromosome 13 presents frequent allelic loss in esophageal squamous cell carcinomas (ESCC). However, no ESCC suppressor gene has been identified from this chromosome. To define common deletion regions that possibly contain the ESCC suppressor gene(s), we performed a mapping of allelic loss in 50 esophageal squamous cell carcinomas using a panel of 25 microsatellite markers on chromosome 13q21-qter, which has rarely been studied for allelic loss. Loss of heterozygosity (LOH) with high frequencies (> or = 50%) was observed at markers D13S1494, D13S1323, D13S248, D13S1315, D13S285, and D13S1295, in which the peak LOH (69.2%) was at locus D13S248. Seven cases presented LOH at three consecutive markers D13S248, D13S1315 and D13S285, 4 of which also displayed LOH at another adjacent marker D13S1295. This overlapping region of deletion covers an interval of 6.36 Mb at 13q33.1-q34, whose deletion has not previously been reported in ESCC. Tumors of grade II showed significantly more frequent LOH at D13S248 than those of grade I. A significantly higher frequency of allelic loss at D13S152 was also found in tumors with lymph node metastasis compared to those without lymph node metastasis. The present study defined a novel region of allelic loss in 13q33-q34. LOH at D13S248 and D13S152 are associated with higher tumor grade and metastasis, respectively.     

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.     

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.     

Allelic loss on chromosome 1 is associated with tumor progression of cervical carcinoma.

BACKGROUND: Alterations in chromosome 1 are common in human malignancies. The frequency of loss of heterozygosity (LOH) on chromosome 1 in cervical carcinoma and its clinical significance are not clearly understood. METHODS: LOH on chromosome 1 was studied in 100 cervical carcinomas by the polymerase chain reaction (PCR) using 29 highly polymorphic microsatellite markers spaced approximately 10 centimorgans apart. Loci with high frequencies of LOH were identified and the findings were correlated with clinicopathologic characteristics. RESULTS: LOH on chromosome 1 at 1 or more loci was detected in 93% of tumors. The frequencies of LOH at locus D1S2829 (1p31), D1S2663 (1p36.3), and D1S2725 (1q25) exceeded 30%, and 12 other loci exhibited frequencies of LOH of 20-30%. Advanced stage tumors had a significantly higher percentage of informative microsatellite markers with LOH than early stage tumors. Of the 29 microsatellite markers studied, 4 loci had a significantly higher frequency of LOH in Stage III and IV tumors than in earlier stage tumors. CONCLUSIONS: Frequent aberrations on chromosome 1 in cervical carcinoma suggest that inactivation of tumor suppressor genes is important in cervical tumorigenesis. Higher frequencies of LOH in Stage III and IV tumors suggest that chromosome 1 changes are late events in cervical carcinoma. The findings of this study are consistent with earlier reports that suggest that tumor suppressor genes are present at 1p36.3 and 1p31. To the authors' knowledge, the high frequency of LOH mapped to 1q25 has not been reported previously. Its significance awaits further clarification.     

Deletion mapping on the short arm of chromosome 1 in Merkel cell carcinoma

Twenty-two Merkel cell carcinoma (MCC) biopsies and six cell lines from 24 patients were examined for loss of heterozygosity (LOH) at 11 loci on 1p and one on 1q, to determine LOH regions on chromosome 1p. Sixteen (73%) tumors had LOH for at least one locus; 14 demonstrated LOH at more than one locus, and 7 (29%) samples had more than one region of loss, with 4 of these having loss at all informative loci on 1p. Three common regions of loss (SRO) were defined by LOH in multiple tumors. Eight samples demonstrated LOH between D1S214 and D1S160 (1p36), seven between D1S234 and D1S186 (1p35), and 11 for the region centromeric of D1S211 and D1S220 (1p32-1p33). Seven samples (29%) demonstrated more than one region of loss. LOH on 1p occurs frequently in MCC and more than one tumor suppressor gene on 1p is likely to play a role in the development of this tumor type.