Deletion Mapping Of Chromosome Research Articles

NDST4 Is a Novel Candidate Tumor Suppressor Gene at Chromosome 4q26 and Its Genetic Loss Predicts Adverse Prognosis in Colorectal Cancer

BackgroundGenomic deletion at tumor suppressor loci is a common genetic aberration in human cancers. The study aimed to explore candidate tumor suppressor genes at chromosome 4q25-q28.2 and to delineate novel prognostic biomarkers associated with colorectal cancer (CRC).MethodsDeletion mapping of chromosome 4q25-q28.2 was conducted in 114 sporadic CRC by loss of heterozygosity study with 11 microsatellite markers. A novel candidate tumor suppressor gene, namely NDST4, was identified at 4q26. Gene expression of NDST4 was investigated in 52 pairs of primary CRC tissues by quantitative reverse transcription-polymerase chain reaction. Allelic loss of NDST4 gene was further determined in 174 colorectal carcinomas by loss of heterozygosity analysis, and then was assessed for clinical relevance.ResultsOne minimal deletion region was delineated between D4S2297 and D4S2303 loci at 4q26, where NDST4 was the only gene that had markedly been downregulated in CRC tumors. By laser capture microdissection, NDST4 RNA expression was demonstrated in colonic epithelial cells, but was undetectable in tumor cells. In total, 30 (57.7%) of 52 colorectal carcinomas showed a dramatic reduction in NDST4 gene expression compared with matched normal mucosae. The genetic loss of NDST4 was significantly associated with advanced pathological stage (P = 0.039) and poorer overall survival of patients (P = 0.036).Conclusions NDST4 gene is a novel candidate tumor suppressor gene in human cancer, and the loss of its function might be involved in CRC progression. In addition, the loss of heterozygosity assay, which was established to determine the allelic loss of NDST4 gene, could be a cost-effective tool for providing a useful biomarker of adverse prognosis in CRC.

Seed development and inheritance studies in apomictic maize-Tripsacum hybrids reveal barriers for the transfer of apomixis into sexual crops

Apomixis in plants covers a variety of cloning systems through seeds of great potential for plant breeding. Among long-standing approaches for crop improvement is the attempt to exploit wild relatives as natural, vast reservoirs for novel genetic variation. With regard to apomixis, maize possesses an apomictic wild relative, Tripsacum, which we used to produce advanced maize-Tripsacum hybrid generations. However, introgression of apomixis in maize has failed so far. In order to understand the hows and whys, we undertook characterization of seed development and inheritance studies in these materials. We show that apomictic seeds suffer from epigenetic loads. Both seed tissues, the endosperm and the embryo, displayed developmental defects resulting from imbalanced parental genomic contributions and aberrant methylation patterns, respectively. Progeny characterization of several maize-Tripsacum hybrid generations allowed significant progress toward the unraveling of the genetics of apomixis. First, chromosome deletion mapping showed that expression of apomixis requires one single Tripsacum chromosome. However, inheritance studies revealed that female gametes inheriting this segment were unequivalent carriers depending on their origin: unreduced gametes transmit a functional segment, whereas progeny derived from reduced ones reproduced sexually. Finally, chromosomal or genomic dosage variation barely affected the apomictic phenotype suggesting no dependency for ploidy in these materials. We conclude that epigenetic information imposes constraints for apomictic seed development and seems pivotal for transgenerational propagation of apomixis. The nature of the triggering mechanisms remains unknown as-yet, but it certainly explains the modest success relative to the development of apomictic maize thus far.

Sons conceived by assisted reproduction techniques inherit deletions in the azoospermia factor (AZF) region of the Y chromosome and the DAZ gene copy number

Deletions in the azoospermia factor (AZF) region of the Y chromosome are frequent in infertile men. The clinical consequences and the mode of inheritance of these deletions are not yet clear. Y chromosome deletion mapping and quantitative PCR analysis of the DAZ-gene copy number, supplemented with haplogroup typing in deleted patients, were performed, in combination with clinical assessments in 264 fathers and their sons conceived by assisted reproduction techniques (ART), and in 168 fertile men with normal sperm concentration. In the ART fathers group, a complete AZFc deletion was detected in 0.4% (1/264). AZFc rearrangements/polymorphisms were found in 6.8% (18/264; 95% CI: 4.4-10.5), which was significantly more frequent (P = 0.021) than in the controls (3/168; 1.8%, 95% CI: 0.6-5.1). All deletions were transmitted to the sons, without any clinical symptoms in early childhood. In the fathers, there was no significant correlation between the DAZ copy number and the severity of spermatogenic failure. AZFc rearrangements/polymorphisms are transmitted to sons and may represent a risk factor for decreased testis function and male subfertility, which needs confirmation in further studies in larger cohorts. However, deletions of two DAZ gene copies are compatible with normal spermatogenesis and fertility.

Deletion Mapping of Chromosome 17 in Benign and Malignant Adrenocortical Tumors Associated with the Arg337His Mutation of the p53 Tumor Suppressor Protein

The human p53 tumor suppressor gene is located at the short arm of chromosome 17. A germinative mutation (Arg337His) in the tetramerization domain of p53 has been frequently identified in Brazilian children with sporadic adrenocortical tumors. Loss of heterozygosity at this region was demonstrated in the majority of the cases. In the present study, we performed deletion mapping of chromosome 17 in 30 adrenocortical tumors from 29 Brazilian patients (15 children and 14 adults). One boy had bilateral adrenocortical tumor. Sixteen patients had the germinative Arg337His mutation. Loss of heterozygosity analysis using six polymorphic microsatellite markers disclosed loss of the entire chromosome 17 in 18 tumors (10 adenomas and eight carcinomas) from 17 patients. The Arg337His mutation was present in 13 of them. Chromosomal instability involving chromosomes 2, 9, and 11 was also found in 47, 47, and 70% of the 17 patients who exhibited chromosome 17 losses, respectively. The concomitant loss of chromosomes 2, 9, 11, and 17 was evidenced exclusively in malignant tumors. Therefore, chromosomal instability involving three or more chromosomes may contribute to define the malignant adrenocortical lesions. In conclusion, we demonstrated a high frequency of biallelic inactivation of p53 derived from two distinct events, the germinative Arg337His mutation and the acquired loss of the entire chromosome 17. In addition, the isolated loss of the entire chromosome 17 did not correlate with aggressive tumor behavior in these patients with adrenocortical tumors.

Analysis of molecular alterations in chromosome 8 associated with the development of uterine cervical carcinoma of Indian patients

Objectives We have been done the detailed deletion mapping of chromosome (chr.) 8p21.3-23 to localize the candidate tumor suppressor gene(s) (TSGs) loci as well as studied the mechanism of activation of c- myc gene, located at chr.8q24.1, by analyzing the amplification/rearrangement/HPV integration within approximately 580 kb of c- myc locus in uterine cervical carcinoma (CaCx) of Indian patients. The association between the deletions in chr.8p21.3-23 and alterations in the c- myc locus has also been analyzed. Methods The deletion mapping of chr.8p21.3-23 was done by 15 microsatellite markers and the alterations in the c- myc locus were analyzed by Southern hybridization using the pal-1/c- myc/mlvi-4/HPV 16/18 probes in seven cervical intraepithelial neoplasia (CIN) and 55 primary uterine cervical carcinoma. The alterations in chr.8p/q have been correlated with the different clinicopathological parameters. Results Three discrete minimal deleted regions with high frequencies of loss of heterozygosity (LOH) (37–43%) were identified in the chr.8p23.1-23.2 (D1), 8p23.1 (D2), and 8p 21.3-22 (D3) regions within 0.41–4.62 Mb. The deletion in the D1 region was significantly associated with the deletion in the D2 region ( P = 0.03), whereas the deletion in D2 was marginally associated with the deletion in the D3 region ( P = 0.07). The alterations in the c- myc locus were seen in 43% of the samples. About 35% of the samples showed coalterations in both arms of chr.8. No significant association was observed with the alterations in chr.8p/q as well as with the different clinicopathological parameters. Conclusions The deletions in chr.8p21.3-23 and the alterations in the c- myc locus are independently associated with the development of CaCx. The D1–D3 regions in chr.8p21.3-23 could harbor candidate TSGs associated with the development of this tumor. The c- myc gene was activated by amplification/rearrangement at the pal-1/c- myc/mlvi-4 loci as well as HPV integration in the pal-1 locus in this tumor.

Differential deletions of chromosome 3p are associated with the development of uterine cervical carcinoma in Indian patients

Background: Deletions in chromosome 3 occur frequently in uterine cervical carcinoma (CA-CX). The common consensus regions deleted during CA-CX development are not well defined, and have not been correlated with...

SIAH1 inactivation correlates with tumor progression in hepatocellular carcinomas.

Accumulation of loss of heterozygosity (LOH) on chromosome 16 is frequently observed in human hepatocellular carcinomas (HCCs). To identify tumor-suppressor genes (TSGs) involved in hepatocarcinogenesis, we performed deletion mapping of chromosome 16 in 59 HCCs. Three commonly deleted regions, located in 16q12.1, 16q22.1, and 16q24.2, were observed. Because there has been no study on LOH at locus 16q12.1 in HCCs, we focused on this region. By searching the Human Genome Database at the National Center for Biotechnology Information web site, we identified 14 known genes in 16q12.1 as TSG candidates. Among these, the expression of SIAH1 was markedly downregulated in HCCs, and inactivation of SIAH1 expression was associated with LOH at 16q12.1. A mutation analysis of SIAH1 revealed no somatic mutations, but one single nucleotide polymorphism was found among the 35 HCCs investigated. Subsequently, we evaluated the relation between SIAH1 expression, confirmed by semiquantitative RT-PCR, and clinicopathological parameters in HCCs. SIAH1 was significantly downregulated in advanced HCCs, including poorly differentiated tumors, larger tumors, and tumors in advanced stages. These findings suggest that inactivation of SIAH1 plays an important role in HCC progression.

Deletion Mapping of Chromosome 1 in Early Onset and Late Onset Breast Tumors – AComparative Study in Eastern India

Younger women exhibit more aggressive pathologic features of breast cancer (BC) compared to their older counterparts. Young age has been shown to be an independent predictor of adverse prognosis. These findings have raised the question of whether these differences are also present at the genetic level. Twenty-five early onset (age < or = 40 years) tumors including 4 bilateral tumors, and 26 late onset (>40 years) breast tumors, including 2 bilateral tumors, were examined for loss of heterozygosity (LOH) at chromosome 1 using 11 polymorphic microsatellite markers. A comparative study revealed high frequencies of LOH in chr. 1p36 (61%), 1p31.3 (40%), 1p21.3 (50%) and 1q22-23.2 (56%) in a younger group, and chr. 1p36 (46%), 1p34.2 (48%), and 1q22-23.2 (52%) in an older group. These differences in LOH frequency in these two age groups were significant for chr. 1p21.3 (p = 0.025) only. These data suggest that the deletion pattern in early onset breast tumors is not fully identical to late onset breast tumors. Similar differential deletion patterns of LOH in the 5 highly deleted regions were seen in premenopausal and postmenopausal groups. An association was seen between LOH at chr. 1p34.2 and chr. 1q22-23.2 and higher grade of the tumors in older women. Among the highly deleted regions, the deletion at chr. 1p36 was found to occur early in both groups because of common allelic loss in the bilateral tumors.

Wheat Genomics: Exploring the Polyploid Model

Wheat is the most consumed grain crop in the world. It is also an excellent model of allopolyploid inheritance. Genomic analysis of wheat is essential for understanding the genetic mechanisms underlying allopolyploid evolution and speciation as well as the biology of agronomically important traits influencing production. In spite of the large genome and polyploidy, researchers have devised novel strategies for in depth structural and functional analysis of the wheat genome. Beginning with the 1920s, wheat has been a model crop for cytogenetic studies, and a plethora of cytogenetic stocks of various types have been developed. Today, a combined cytogenetic and molecular approach has greatly advanced wheat genome analysis. The comparison of physical maps of wheat chromosomes based on chromosome deletion mapping with molecular genetic linkage maps led to the notion that genes were not distributed at random throughout the wheat genome, but rather exist in gene-rich recombination hot spots along the chromosomes. Recent construction and sequencing of local BAC contigs has verified this hypothesis, suggesting that most genes in wheat are amenable to positional cloning. Wheat is now moving into the functional genomics era as researchers focus on the expressed portion of the wheat genome. A database of expressed sequence tags (ESTs) is growing rapidly as researchers work to assign gene function. High-throughput production and identification of mutants will be necessary for the assignment of function to the many genes being discovered in wheat.

Identification of candidate liver tumor suppressor genes from human 11p11.2-p12.

We have previously described a functional model for identification of human liver tumor suppressor genes in which human chromosome 11 was introduced into rat liver epithelial tumor cell lines via microcell-mediated chromosome transfer, producing microcell hybrid (MCH) cell lines that exhibit suppression of tumorigenicity in vivo. Chromosome deletion mapping studies identified a 950-kb region of 11p11.2-p12 that was retained in all suppressed MCH cell lines, suggesting that this region may harbor one or more genes with liver tumor suppressor function. In this study, we generated a comprehensive transcription map of the 11p11.2-p12 liver tumor suppressor region through examination of 142 expressed sequence tag (EST) markers among a group of suppressed MCH cell lines. Of 142 ESTs examined, 19 were localized within the 11p11.2-p12 liver tumor suppressor region. RT-PCR analysis of gene expression for these 19 ESTs among an index panel of suppressed MCH cell lines (n = 3) identified 11 potential candidate liver tumor suppressor genes. Examination of candidate gene expression among six additional suppressed MCH cell lines reduced the number of potential candidate genes to three (stSG30184, stSG10014, and stSG29748). Northern blot analysis of suppressed MCH cell lines and derived tumor cell lines suggested stSG30184 as the best candidate liver tumor suppressor gene. The 3.7 kb stSG30184 transcript was expressed by all suppressed MCH cell lines, but expression was extinguished coordinately with reexpression of tumorigenicity by these cells, consistent with a tumor suppressor gene. Subsequent characterization of this EST indicates that it is a novel transcript with expression in a broad range of tissue types. Further characterization of the genes identified in this study will provide a greater understanding of their role in the molecular pathogenesis of neoplastic liver disease.

Frequent loss of heterozygosity at the Hcr1 (hepatocarcinogenesis resistance) locus on chromosome 10 in primary hepatocellular carcinomas from LFF1 rat strain.

Hepatocarcinogenesis sensitivity (Hcs1, 2) and resistance (Hcr1-3) loci have been identified by linkage analysis on rat chromosomes 7 and 1, and 10, 4, and 8, respectively. Cytogenetic studies documented deletions on chromosomes 3 and 6 of neoplastic rat hepatocytes. Hepatocellular carcinomas (HCCs) were produced in F1 hybrid rats between Long-Evans (LE) and Fisher 344 (F344) rats. Scanning of the above chromosomes for loss of heterozygosity (LOH) showed allelic imbalance (AI) at multiple regions on chromosomes 6, 7, and 10q. Detailed deletion mapping of chromosome 10 localized a putative suppressor Hcr1 gene to within a 3.2-cM interval flanked by D10Rat51 and D10Rat121. Two other distinct regions with frequent AIs were found inside the Hcr1 locus, at marker loci including DNaseI and Mrp genes, and in a segment including 4 consecutive markers (D10Rat64, D10Rat182, D10Rat113, D10Rat216). In 40% of HCCs, AI was seen at the p53 locus. AI on chromosome 7 occurred at the Hcs1 locus, where is located c-myc, which is amplified in HCCs, suggesting allelic gain. Most AIs occurred in poorly/moderately differentiated carcinomas, and a few events were seen in well-differentiated tumors on chromosomes 7 and 10. These data suggest that alteration of a cluster of oncosuppressor genes on 10q is important for HCC progression. The existence of AI on segments of rat chromosomes 6, 7, and 10, syntenic to chromosomal segments of human HCCs where chromosomal gains or deletions occur, suggests a commonality of some molecular events in the pathogenesis of HCCs in rats and humans. Our map provides information toward cloning putative oncosuppressor genes associated with this carcinoma.

CDKN2A Mutation Analysis, Protein Expression, and Deletion Mapping of Chromosome 9p in Conventional Clear-Cell Renal Carcinomas : Evidence for a Second Tumor Suppressor Gene Proximal to CDKN2A

Inactivation of tumor suppressor genes on chromosome 9p is considered a critical event in renal cell carcinoma pathogenesis. Alterations of CDKN2A on 9p21 have been reported in renal cancer cell lines, but their relevance for primary renal carcinomas is unclear. Loss of heterozygosity (LOH) was analyzed by using four polymorphic microsatellites at D9S970 (9p12-9p13), D9S171 (9p13), D9S1748 (9p21), and D9S156 (9p21) in 113 primary conventional clear-cell renal cell carcinomas (CRCCs). Allelic deletion was detected in 21 of 88 informative CRCCs (24%) with the highest rate of LOH being observed at D9S171 on 9p13 (20%). Chromosome 9p LOH was associated with short tumor-specific survival in stage pT3 RCC (P = 0.01). Fluorescence in situ hybridization analysis of 54 CRCCs revealed no homozygous CDKN2A deletions indicating that this mechanism of CDKN2A inactivation is rare in CRCC. Sequencing of 113 CRCCs showed that 13 tumors (12%) had a 24-bp deletion abrogating codons 4 through 11 of CDKN2A. Immunohistochemical CDKN2A expression was absent in normal renal tissue and was only detected in six of 382 CRCCs (1.5%) on a renal tumor microarray. These data suggest that CDKN2A alterations are present in a small subset of CRCCs and a second, yet unknown tumor suppressor gene proximal to the CDKN2A locus, may play a role in CRCC development.

High‐resolution deletion mapping of chromosome 14 in stromal tumors of the gastrointestinal tract suggests two distinct tumor suppressor loci

High‐resolution deletion mapping of chromosome 14 in stromal tumors of the gastrointestinal tract suggests two distinct tumor suppressor loci

High-resolution deletion mapping of chromosome 14 in stromal tumors of the gastrointestinal tract suggests two distinct tumor suppressor loci

DNA copy number losses at chromosome arm 14q are the most frequently occurring aberrations in gastrointestinal stromal tumors (GISTs). To characterize the deletion at 14q, we performed comparative genomic hybridization (CGH) and high-resolution deletion mapping using a panel of 32 polymorphic microsatellite markers in 30 GISTs. The GISTs were classified according to their metastatic potential and mitotic counts into 15 low-risk and 15 high-risk tumors. Losses with a minimal common overlapping region at 14q12-q24 were detected by CGH in 16 tumors (53) (nine low-risk and seven high-risk). Investigation with microsatellite markers was informative in 690 analyses (72%). Loss of heterozygosity (LOH) with at least one marker was detected in 279 analyses in 24 tumors (80%). Deletions were equally frequent in low-risk and high-risk GISTs. Two common deletion regions were identified at 14q11.1-q12 and 14q23-q24.3. The highest frequencies of deletions were seen in regions corresponding to markers D14S283 (20/28, 71%) at 14q11.1-q12 and D14S258 (17/27, 63%) at 14q23-q24, suggesting that these are two tumor suppressor loci.

A group of schwannomas with interstitial deletions on 22q located outside the NF2 locus shows no detectable mutations in the NF2 gene.

Schwannomas are tumors arising mainly at cranial and spinal nerves. Bilateral vestibular schwannoma is the hallmark of neurofibromatosis type2 (NF2). The NF2 gene has been cloned and comprehensive analysis of its mutations in schwannomas shows that up to 60% of tumors carry inactivating mutations. Thus, the genetic mechanism behind the development of more than 40% of schwannomas without NF2 mutations is unknown. We have therefore studied tumor tissue from 50 human schwannomas by allelotyping and have found chromosome 22 deletions in over 80% of the cases. We detected 14 cases (27%) that revealed partial deletions of one copy of chromosome 22, i.e., terminal and/or interstitial deletions. We sequenced the NF2 gene in seven of these tumors and detected only one case with mutations. The deletion mapping of chromosome 22 in tumors with partial deletions indicates that several regions, in addition to the NF2 locus, harbor genes involved in schwannoma tumorigenesis. Our findings suggest that heterogeneity in the mechanisms leading to the development of schwannomas probably exists. These findings are in agreement with the recent analysis of schwannomas from familial and sporadic cases of schwannomatosis and point to a possible role of an additional gene, which, in cooperation with the NF2 tumor suppressor, causes schwannomas.

Deletion mapping of chromosome 4 in head and neck squamous cell carcinoma.

Genomic deletions involving chromosome 4 have recently been implicated in several human cancers. To identify and characterize genetic events associated with the development of head and neck squamous cell carcinoma (HNSCC), a fine mapping of allelic losses associated with chromosome 4 was performed on DNA isolated from 27 matched primary tumor specimens and normal tissues. Loss of heterozygosity (LOH) of at least one chromosome 4 polymorphic allele was seen in the majority of tumors (92%). Allelic deletions were confined to short arm loci in four tumors and to the long arm loci in 12 tumors, suggesting the presence of two regions of common deletion. One region of frequent deletion was centered at D4S405 on 4p and included the loci D4S1546 to D4S428 in approximately 41% of the tumors. The common region of deletion on 4q was more complex and extended from D4S1571 to D4S1573. Frequent genetic alterations were observed within this region (4q25) and one marker, D4S407, exhibited a high frequency of LOH (>75%). These results indicate that alterations of chromosome 4 regions are associated with HNSCC tumorigenesis and further localizes the regions that may harbor tumor suppressor genes.

Deletion mapping of chromosome 2 in human lung carcinoma.

Sixty-three non-small cell lung carcinomas (NSCLCs) and 20 small cell lung carcinomas (SCLCs) were examined for loss of heterozygosity (LOH) on chromosome 2. Fifteen highly polymorphic dinucleotide markers spanning both the short and long arms of chromosome 2 were selected for a polymerase chain reaction (PCR)-based fine mapping. They included a DNA marker localized in the homozygously deleted region at 2q33, which we previously identified in an SCLC cell line. LOH on chromosome arm 2q was detected in 23/63 (37%) of NSCLC and 6/20 (30%) of SCLC, while LOH on 2p was observed in 14/56 (25%) and 4/17 (24%), respectively. There were two commonly deleted regions mapped to 2q32-q37 and 2p16-pter, and the homozygously deleted region at 2q33 was in the commonly deleted region on 2q. In NSCLC, the incidence of LOH on 2p and 2q was significantly higher in brain metastases than in primary tumors (P = 0.005 and 0.001, respectively). In addition, LOH on chromosome arm 2q occurred more frequently in moderately/poorly differentiated tumors than in well-differentiated tumors (P = 0.046). These results suggested that inactivation of tumor suppressor genes on chromosome 2 is involved in the phenotypic alterations of NSCLC cells into more aggressive ones.

Deletion mapping of chromosome 10 in human glioma.

We analyzed DNAs from 35 gliomas (27 malignant, grades III and IV; 8 less malignant, grades I and II) for loss of heterozygosity (LOH) using microsatellite sequences on chromosome 10 as polymorphic markers. An LOH was found in 8 of 11 (73%) glioblastomas (grade IV) and 4 of 16 (25%) grade III gliomas, but not in the less malignant types. We detected three commonly deleted regions. One was located in a telomeric region of 10p and the others were relatively large regions of 10q. Our results suggested that three putative tumor suppressor genes on chromosome 10 are involved in the malignant progression of gliomas.

Deletions of the long arm of chromosome 10 in progression of follicular thyroid tumors.

Previous studies of follicular thyroid tumors have shown loss of heterozygosity (LOH) on the short arm of chromosome 3 in carcinomas, and on chromosome 10 in atypical adenomas and carcinomas, but not in common adenomas. We studied LOH on these chromosomal arms in 15 follicular thyroid carcinomas, 19 atypical follicular adenomas and 6 anaplastic (undifferentiated) carcinomas. Deletion mapping of chromosome 10 using 15 polymorphic markers showed that 15 (37.5%) of the tumors displayed LOH somewhere along the long arm. Thirteen of these tumors showed deletions involving the telomeric part of chromosome 10q, distal to D10S187. LOH on chromosome 3p was found in 8 (20%) cases. Seven of these also showed LOH on chromosome 10q. In eight cases LOH was seen on chromosome 10q but not 3p. In comparison, the retinoblastoma gene locus at chromosome 13q showed LOH in 22% of the tumors. Most of these also had deletions on chromosome 10q. The results indicate that a region at the telomeric part of 1Oq may be involved in progression of follicular thyroid tumors.

Deletion mapping of chromosome II in carcinoma of the bladder

Deletions of the short arm of chromosome 11 have been identified by both cytogenetic and molecular criteria in bladder and other types of solid tumor, indicating the presence of one or more suppressor loci in this region. To localize the 11p deletion target(s) more precisely and to screen for loss of heterozygosity (LOH) on the long arm of the chromosome, 100 bladder tumors were analyzed for LOH on chromosome 11 using restriction fragment length polymorphisms (RFLPs) and microsatellite markers mapped to both 11p and 11q. Thirty-four tumors were found to have LOH at 1 or more loci. Of these, 17 had LOH restricted to 11p, 13 had LOH of both 11p and 11q, and 4 had LOH of 11q only. Eight tumors showed LOH at all informative loci indicating probable loss of an entire copy of chromosome 11. A common region of deletion was defined on 11p between D11S922 (11p15.5) and D11S569 (11p15.1-15.2). This region does not include the HRAS or WT1 loci (at 11p15.5 and 11p13, respectively). Seventeen tumors had LOH on 11q, 4 of which had LOH on 11q only. The common region of deletion on 11q was between FGF3 and D11S490 (11q13-q23.2). Two tumors showed LOH on both 11p and 11q with a clear region of retention of heterozygosity between, indicating the existence of two deletion targets on chromosome 11.