[Da Vinci robot-assisted pylorus and vagus nerve-preserving partial gastrectomy for gastric cancer].

Objective: To investigate the safety and feasibility of Da Vinci robot-assisted pylorus and vagus nerve-preserving partial gastrectomy for gastric cancer. Methods: In this study, descriptive case series method was used to retrospectively analyze the data of 3 patients with gastric cancer who underwent Da Vinci robot-assisted pylorus and vagus nerve-preserving partial gastrectomy in the First Affiliated Hospital of Dalian Medical University from December 2020 to February 2021. The linear layout was adopted for the setting of trocar, and the co-axial direction was the line connecting the umbilicus and splenic hilum. The inferior pyloric arteries and veins need to be preserved. The center was the bifurcation of the right gastroepiploic vessel and the inferior pyloric vessel. Dissection and exposure were performed from the upper, lower, right and left sides, and ventral and dorsal sides to complete the dissection of the inferior pyloric lymph nodes. The superior border of the pancreas was treated by the right diaphragmatic crus approach, the left retroperitoneal approach and the esophageal approach to determine the distribution of the posterior vagal trunk and its branches, and to determine the anatomical relationship with the left gastric artery. The left gastric artery was cut off while the celiac branch of vagus nerve and cardia branch of left gastric artery were preserved. Lymph node dissection was performed on the lateral side of nerve fibers around the blood vessels. Result: All the 3 patients successfully completed the robotic surgery without conversion to laparoscopy or laparotomy. The operation time was (340.0±26.4) (300-390) minutes, the intraoperative blood loss was (13.3±3.3) (10-20) ml, the number of dissected lymph nodes was 26.7±3.9 (19-32), the length of pylorus canal preserved was (3.3±0.3) (3-4) cm, the distal margin was (2.3±0.3) (2-3) cm, and the proximal margin was (3.0±0.6) (2-4) cm. No postoperative complications occurred in all the 3 patients. The first flatus time was 2-3 days after operation, and the postoperative hospital stay was 6-7 days. The operation cost of the 3 patients was (40±7) (33-53) thousand yuan. Conclusion: Da Vinci robot-assisted pylorus and vagus nerve-preserving partial gastrectomy is safe and feasible.

[The impact of surgical treatment on the life quality of patients with locally advanced hypopharyngeal carcinoma].

Objective: To explore the impact of surgical treatment on the life quality of patients with locally advanced hypopharyngeal carcinoma. Methods: A retrospective analysis of the clinical data of 21 patients with advanced hypopharyngeal carcinoma who underwent surgery at the Shenzhen Hospital of Chinese Academy of Medical Sciences Cancer Hospital from January 1, 2017 to December 31, 2019 was conducted. There were 3 patients with recurrence after radiotherapy and chemotherapy, 4 cases of postoperative recurrence, 3 cases of postoperative recurrence after radiotherapy and chemotherapy. Three cases were hypopharyngeal carcinoma with esophageal carcinoma and 8 cases were stage Ⅳ hypopharyngeal carcinoma. Among them, 3 cases were repaired by stomach, 4 cases by free jejunum, 2 case by great saphenous vein for internal carotid artery, 1 case by artificial blood vessel for internal carotid artery, 5 cases by transfer of pectoralis major musculocutaneous flap and 2 cases by transfer of submental island flap. The 21 patients were scored using the European Cancer Research and Treatment Organization's Quality of Life Head and Neck Tumor Special Scale (EORTC QLQ-H&N35) on the 3 months before and after surgery, and the changes in postoperative life quality were compared. Results: The preoperative life quality score of 21 patients was (56.86±7.95) points and life quality score of 3 months after operation was (50.93±7.91) points. The postoperative life quality was significantly improved (P<0.05). The improvement of the postoperative life quality of the patients mainly included the improvements of the head and neck pain, swallowing function, diet, taking analgesics and indwelling nasal feeding tubes. The preoperative scores were (7.58±1.56) points, (8.46±1.63) points, (7.94±0.43) points, (1.76±0.12) points and (1.86±0.28) points, respectively, while the scores of 3 months after operation were (5.02±1.23) points, (6.28±1.58) points, (6.34±0.36) points , (1.12±0.08) points and (1.24±0.18) points, the differences were statistically significant (all P<0.05). Conclusion: The flexible selection of flap repair for locally advanced hypopharyngeal carcinoma is still feasible, and surgery can improve the life quality of patients.

[Association between both maternal and fetal angiotensinogen gene single nucleotide polymorphism and preeclampsia/eclampsia].

Objective: To explore the association between preeclampsia/eclampsia and maternal and fetal angiotensinogen SNPs. Methods: From January 2008 to October 2015, a case-parents/mother-control designed study was conducted among 347 preeclampsia/eclampsia cases and 700 controls to collect related information on their demographic characteristics and to detect the related angiotensinogen SNPs' genotypes. Both log-linear and unconditional logistic regression methods were employed to investigate the genetic effects of maternal/fetal angiotensinogen SNPs on preeclampsia/eclampsia. Multivariate binary unconditional logistic regression model and covariance were used to analyze the relationship between BMI before pregnancy, weight gain during pregnancy and overweight and obesity in preschool children. Results: Both fetal angiotensinogen rs3789679 GA and AA genotype were associated with the reduced risks of preeclampsia/eclampsia, with ORs as 0.73 (95%CI: 0.55-0.96) and 0.62 (95%CI: 0.39-0.98), respectively. For fetal angiotensinogen rs2493132, individuals that carrying the TT genotype, presented a positive association with the risk of preeclampsia/eclampsia, with OR as 1.60 (95%CI: 1.08-2.37). However, these associations were not statistically significant after the correction of the false discovery rate. It was observed that fetal rs3789679 could reduce the risk of preeclampsia/eclampsia (OR=0.73, 95%CI: 0.55-0.96) under the dominant model (GA+AA/GG) while fetal rs2493132 increased the risk of preeclampsia/eclampsia (OR=1.66, 95%CI: 1.13-2.44) under the recessive model (TT/CC+CT). Maternal rs5051 presented an association with preeclampsia/eclampsia (OR=1.33, 95%CI: 1.01-1.76) under the dominant model (TC+CC/TT). Conclusions: Results from the dominant model showed that both fetal rs3789679 GA and AA genotype reduced the risk of preeclampsia/eclampsia and maternal rs5051 TC while CC genotype increased the risk of preeclampsia/eclampsia. Fetal rs2493132 TT genotype seemed to be associated with the risk of preeclampsia/eclampsia under the recessive model.

A retrospective clinical study of bevacizumab combined with gemcibabine or paclitaxel in the treatment of recurrent ovarian cancer.

BACKGROUND: Bevacizumab, a recombinant humanized monoclonal antibody that blocks angiogenesis by inhibiting vascular endothelial growth factor A, was described to be effective in the treatment of recurrent or platinum-resistance ovarian cancer. The present retrospective study was performed to further evaluate the clinical efficacy and toxicity of bevacizumab in the treatment of Chinese recurrent ovarian cancer patients who had been previously treated by platinum-based chemotherapy. MATERIALS AND METHODS: We reviewed the hospital database and finally included 26 recurrent ovarian cancer patients who were treated with bevacizumab combined with gemcibabine or paclitaxel or single agent. All included patients received >3 cycle of bevacizumab treatment. The tumor response, overall survival, and toxicities were documented. RESULTS: Under the treatment of bevacizumab combined with gemcibabine or paclitaxel, 2 complete response (7.7%), 8 partial response (30.8%), 7 stable disease (26.9%) and 9 progression disease (34.6%) was documented with the objective response rate of 38.5% and disease control rate of 65.4%. The median overall survival from the first application of bevacizumab was 15.3 months [Figure 1] for all of the 26 patients. The median overall survival time was 16.2 and 14.0 months for bevacizumab + gemcitabine and bevacizumab + paclitaxel treatment schedule respectively. The overall survival was not different between bevacizumab + gemcitabine and bevacizumab + paclitaxel treatment regimen hazard ratio = 0.80 (95% confidence interval: 0.32-2, P = 0.64). The hypertension and proteinuria were the major bevacizumab related toxicities. CONCLUSIONS: Bevacizumab combined with gemcibabine or paclitaxel was a promising treatment schedule for platinum-resistance recurrent ovarian cancer.

A screening trial of Helicobacter pylori-specific antigen tests in saliva to identify an oral infection.

OBJECTIVE: Helicobacter pylori infection places a heavy burden on medical and economic resources. Standard diagnosis requires the presence of established H. pylori gastric disease. STUDY DESIGN AND SETTING: A multicenter screening trial assessing 2 immunochromatographic H. pylori antigen oral tests was carried out with 201 participants. The analysis also included a urea breath test (UBT), a Campylobacter-like organism test, silver stain, culture, serology, and stool tests. RESULTS: The participants were grouped into UBT positive (UBT+) and UBT negative (UBT-) people, using conventional methods with congruent clusters based on p values from McNemar's paired χ2 analysis and 95% CI estimates. Both oral tests were also positive in 82% of the seropositive UBT- people. However, oral antigen and seroprevalence divided UBT- people into 2 statistically separate CI subgroups: the UBT- symptomatic (highly positive) group and the UBT- asymptomatic (mostly negative) group. 90.5% of all people whose oral tests were both negative were also UBT-. CONCLUSIONS: Saliva H. pylori antigen is an important indicator in UBT- asymptomatic patients. Currently, its clinical significance remains uncertain, but saliva may be a reservoir from where H. pylori is transmitted to the stomach. In symptomatic patients, it is strongly associated with stomach infection.

Novel transglutaminase-1 mutations and genotype-phenotype investigations of 104 patients with autosomal recessive congenital ichthyosis in the USA.

BACKGROUND: Autosomal recessive congenital ichthyosis (ARCI) is a rare hereditary disorder of cornification. Mutations in the transglutaminase-1 (TGM1) gene, which encodes for the epidermal enzyme transglutaminase-1 (TGase-1), are one of the causes of ARCI. METHODS: The TGM1 mutation spectrum was characterised and genotype-phenotype correlations investigated in 104 patients with ARCI ascertained through the National Registry for Ichthyosis and Related Disorders in the USA. Methods: Germline mutations in TGM1 were identified in 55% (57/104) of patients with ARCI. Arginine residues in TGase-1 were mutated in 39% (22/57) of patients overall and 54% (20/37) of those with missense mutations. In total, 55% (12/22) of missense mutations were within CpG dinucleotides and 92% (11/12) of these mutations were C-->T or G-->A transitions. The genotype-phenotype investigation found that ARCI with TGM1 mutations was significantly associated with presence of collodion membrane at birth (p = 0.006), ectropion (p = 0.001), plate-like scales (p = 0.005) and alopecia (p = 0.001). Patients who had at least one mutation predicted to truncate TGase-1 were more likely to have more severe hypohidrosis (p = 0.001) and overheating (p = 0.0007) at onset of symptoms than were those with exclusively TGM1 missense mutations. A logistic model was developed, which predicted that individuals with collodion membrane, alopecia and/or eye problems are about four times more likely to have TGM1 mutations than patients without these findings. CONCLUSION: This is the largest investigation of patients with ARCI to date. It expands the TGM1 mutation spectrum and confirms that despite genetic and phenotypic heterogeneity in ARCI, TGM1 is the main causative gene for this disorder. The high frequency of mutated arginine codons in TGM1 may be due to the deamination of CpG dinucleotides.

BHD mutations, clinical and molecular genetic investigations of Birt-Hogg-Dubé syndrome: a new series of 50 families and a review of published reports.

BACKGROUND: Birt-Hogg-Dubé syndrome (BHDS) (MIM 135150) is an autosomal dominant predisposition to the development of follicular hamartomas (fibrofolliculomas), lung cysts, spontaneous pneumothorax, and kidney neoplasms. Germline mutations in BHD are associated with the susceptibility for BHDS. We previously described 51 BHDS families with BHD germline mutations. OBJECTIVE: To characterise the BHD mutation spectrum, novel mutations and new clinical features of one previously reported and 50 new families with BHDS. METHODS: Direct bidirectional DNA sequencing was used to screen for mutations in the BHD gene, and insertion and deletion mutations were confirmed by subcloning. We analysed evolutionary conservation of folliculin by comparing human against the orthologous sequences. RESULTS: The BHD mutation detection rate was 88% (51/58). Of the 23 different germline mutations identified, 13 were novel consisting of: four splice site, three deletions, two insertions, two nonsense, one deletion/insertion, and one missense mutation. We report the first germline missense mutation in BHD c.1978A>G (K508R) in a patient who presented with bilateral multifocal renal oncocytomas. This mutation occurs in a highly conserved amino acid in folliculin. 10% (5/51) of the families had individuals without histologically confirmed fibrofolliculomas. Of 44 families ascertained on the basis of skin lesions, 18 (41%) had kidney tumours. Patients with a germline BHD mutation and family history of kidney cancer had a statistically significantly increased probability of developing renal tumours compared to patients without a positive family history (p = 0.0032). Similarly, patients with a BHD germline mutation and family history of spontaneous pneumothorax had a significantly increased greater probability of having spontaneous pneumothorax than BHDS patients without a family history of spontaneous pneumothorax (p = 0.011). A comprehensive review of published reports of cases with BHD germline mutation is discussed. CONCLUSION: BHDS is characterised by a spectrum of mutations, and clinical heterogeneity both among and within families.

Fumarate hydratase enzyme activity in lymphoblastoid cells and fibroblasts of individuals in families with hereditary leiomyomatosis and renal cell cancer.

BACKGROUND: Hereditary leiomyomatosis and renal cell cancer (HLRCC) is the autosomal dominant heritable syndrome with predisposition to development of renal cell carcinoma and smooth muscle tumours of the skin and uterus. OBJECTIVE: To measure the fumarate hydratase (FH) enzyme activity in lymphoblastoid cell lines and fibroblast cell lines of individuals with HLRCC and other familial renal cancer syndromes. METHODS: FH enzyme activity was determined in the whole cell, cytosolic, and mitochondrial fractions in 50 lymphoblastoid and 16 fibroblast cell lines including cell lines from individuals with HLRCC with 16 different mutations. RESULTS: Lymphoblastoid cell lines (n = 20) and fibroblast cell lines (n = 11) from individuals with HLRCC had lower FH enzyme activity than cells from normal controls (p<0.05). The enzyme activity in lymphoblastoid cell lines from three individuals with mutations in R190 was not significantly different from individuals with other missense mutations. The cytosolic and mitochondrial FH activity of cell lines from individuals with HLRCC was reduced compared with those from control cell lines (p<0.05). There was no significant difference in enzyme activity between control cell lines (n = 4) and cell lines from affected individuals with other hereditary renal cancer syndromes (n = 22). CONCLUSIONS: FH enzyme activity testing provides a useful diagnostic method for confirmation of clinical diagnosis and screening of at-risk family members.

Novel mutations in FH and expansion of the spectrum of phenotypes expressed in families with hereditary leiomyomatosis and renal cell cancer.

BACKGROUND: Hereditary leiomyomatosis and renal cell cancer (HLRCC; OMIM 605839) is the predisposition to develop smooth muscle tumours of the skin and uterus and/or renal cancer and is associated with mutations in the fumarate hydratase gene (FH). Here we characterise the clinical and genetic features of 21 new families and present the first report of two African-American families with HLRCC. METHODS: Using direct sequencing analysis we identified FH germline mutations in 100% (21/21) of new families with HLRCC. RESULTS: We identified 14 germline FH mutations (10 missense, one insertion, two nonsense, and one splice site) located along the entire length of the coding region. Nine of these were novel, with six missense (L89S, R117G, R190C, A342D, S376P, Q396P), one nonsense (S102X), one insertion (111insA), and one splice site (138+1G>C) mutation. Four unrelated families had the R58X mutation and five unrelated families the R190H mutation. Of families with HLRCC, 62% (13/21) had renal cancer and 76% (16/21) cutaneous leiomyomas. Of women FH mutation carriers from 16 families, 100% (22/22) had uterine fibroids. Our study shows that expression of cutaneous manifestations in HLRCC ranges from absent to mild to severe cutaneous leiomyomas. FH mutations were associated with a spectrum of renal tumours. No genotype-phenotype correlations were identified. CONCLUSIONS: In combination with our previous report, we identify 31 different germline FH mutations in 56 families with HLRCC (20 missense, eight frameshifts, two nonsense, and one splice site). Our FH mutation detection rate is 93% (52/56) in families suspected of HLRCC.

Functional properties of a new voltage-dependent calcium channel alpha(2)delta auxiliary subunit gene (CACNA2D2).

We have positionally cloned and characterized a new calcium channel auxiliary subunit, alpha(2)delta-2 (CACNA2D2), which shares 56% amino acid identity with the known alpha(2)delta-1 subunit. The gene maps to the critical human tumor suppressor gene region in chromosome 3p21.3, showing very frequent allele loss and occasional homozygous deletions in lung, breast, and other cancers. The tissue distribution of alpha(2)delta-2 expression is different from alpha(2)delta-1, and alpha(2)delta-2 mRNA is most abundantly expressed in lung and testis and well expressed in brain, heart, and pancreas. In contrast, alpha(2)delta-1 is expressed predominantly in brain, heart, and skeletal muscle. When co-expressed (via cRNA injections) with alpha(1B) and beta(3) subunits in Xenopus oocytes, alpha(2)delta-2 increased peak size of the N-type Ca(2+) currents 9-fold, and when co-expressed with alpha(1C) or alpha(1G) subunits in Xenopus oocytes increased peak size of L-type channels 2-fold and T-type channels 1.8-fold, respectively. Anti-peptide antibodies detect the expression of a 129-kDa alpha(2)delta-2 polypeptide in some but not all lung tumor cells. We conclude that the alpha(2)delta-2 gene encodes a functional auxiliary subunit of voltage-gated Ca(2+) channels. Because of its chromosomal location and expression patterns, CACNA2D2 needs to be explored as a potential tumor suppressor gene linking Ca(2+) signaling and lung, breast, and other cancer pathogenesis. The homologous location on mouse chromosome 9 is also the site of the mouse neurologic mutant ducky (du), and thus, CACNA2D2 is also a candidate gene for this inherited idiopathic generalized epilepsy syndrome.

PANORAMA: an integrated Web-based sequence analysis tool and its role in gene discovery.

As the exponential growth of DNA sequence information in databases continues, the task of converting this deposited information into knowledge becomes more dependent on integrative sequence analysis and visualization tools. PANORAMA is an Internet-accessible software package that performs a variety of informatics analyses on a given DNA sequence and returns a visual and interactive representation of the results. Its design is modular, so that further sequence analysis tools can be integrated with minimal effort. The utility of PANORAMA is demonstrated in the analysis of 650 kb of human genomic DNA from chromosome region 3p21.3, a region of potential tumor suppressor genes involved in lung cancer, breast cancer, and other forms of cancer. PANORAMA aided in the discovery of genes and alternate splice forms of known exons, in the demarcation of intron-exon boundaries, and in the identification of promoter regions and polymorphisms, all of which contributed to a better understanding of the region. PANORAMA is available on the World Wide Web at http://atlas.swmed.edu.

Two single nucleotide polymorphisms (SNPs) in the CALL gene for association studies with IQ.

A number of genes underlie the molecular bases of intelligence. Among these is probably CALL, a novel member of the L1 gene family of neural cell adhesion molecules. By using the single strand conformation polymorphism (SSCP) protocol, we screened the regions of the CALL gene corresponding to the 5' and 3' untranslated regions (UTRs) of the CALL mRNA, searching for polymorphisms that could be useful in association studies in the field of intelligence. We report the finding of T-to-A and T-to-C single nucleotide polymorphisms (SNPs) in the 3' UTR of CALL. These SNPs have an index of heterozygosity of 0.13 and 0.10, respectively. Research is in progress to understand the association between these variants and high IQ.

CALL gene is haploinsufficient in a 3p- syndrome patient.

The 3p- syndrome results from deletion of a terminal segment of the short arm of one chromosome 3 (3p25-->pter), and is characterized by multiple congenital anomalies and mental retardation. Due to its variable expression, it is assumed this disorder is a contiguous gene syndrome with an undefined number of genes contributing to the phenotype. In an effort to discover genes contributing to mental defects in 3p- syndrome, we determined whether the CALL gene, mapped to 3p26.1 and coding for a neural recognition molecule, is deleted in a boy with this disorder. We found that the break in this patient is distal to the VHL gene, removing D3S18 and the CALL loci. The deletion of one copy of the CALL gene might be responsible for mental defects in patients with 3p- syndrome. Am. J. Med. Genet. 86:482-485, 1999. Published 1999 Wiley-Liss, Inc.

In silico-initiated cloning and molecular characterization of a novel human member of the L1 gene family of neural cell adhesion molecules.

To discover genes contributing to mental retardation in 3p- syndrome patients we have used in silico searches for neural genes in NCBI databases (dbEST and Uni-Gene). An EST with strong homology to the rat CAM L1 gene subsequently mapped to 3p26 was used to isolate a full-length cDNA. Molecular analysis of this cDNA, referred to as CALL (cell adhesion L1-like), showed that it is encoded by a chromosome 3p26 locus and is a novel member of the L1 gene family of neural cell adhesion molecules. Multiple lines of evidence suggest CALL is likely the human ortholog of the murine gene CHL1: it is 84% identical on the protein level, has the same domain structure, same membrane topology, and a similar expression pattern. The orthology of CALL and CHL1 was confirmed by phylogenetic analysis. By in situ hybridization, CALL is shown to be expressed regionally in a timely fashion in the central nervous system, spinal cord, and peripheral nervous system during rat development. Northern analysis and EST representation reveal that it is expressed in the brain and also outside the nervous system in some adult human tissues and tumor cell lines. The cytoplasmic domain of CALL is conserved among other members of the L1 subfamily and features sequence motifs that may involve CALL in signal transduction pathways.

Down-regulation of transmembrane carbonic anhydrases in renal cell carcinoma cell lines by wild-type von Hippel-Lindau transgenes.

To discover genes involved in von Hippel-Lindau (VHL)-mediated carcinogenesis, we used renal cell carcinoma cell lines stably transfected with wild-type VHL-expressing transgenes. Large-scale RNA differential display technology applied to these cell lines identified several differentially expressed genes, including an alpha carbonic anhydrase gene, termed CA12. The deduced protein sequence was classified as a one-pass transmembrane CA possessing an apparently intact catalytic domain in the extracellular CA module. Reintroduced wild-type VHL strongly inhibited the overexpression of the CA12 gene in the parental renal cell carcinoma cell lines. Similar results were obtained with CA9, encoding another transmembrane CA with an intact catalytic domain. Although both domains of the VHL protein contribute to regulation of CA12 expression, the elongin binding domain alone could effectively regulate CA9 expression. We mapped CA12 and CA9 loci to chromosome bands 15q22 and 17q21.2 respectively, regions prone to amplification in some human cancers. Additional experiments are needed to define the role of CA IX and CA XII enzymes in the regulation of pH in the extracellular microenvironment and its potential impact on cancer cell growth.

Cloning of a breast cancer homozygous deletion junction narrows the region of search for a 3p21.3 tumor suppressor gene.

Chromosome 3p abnormalities and allele loss are frequent in lung and breast cancers, and several lung cancer cell lines exhibit homozygous deletions of 3p indicating potential sites of tumor suppressor genes at regions 3p21.3, 3p14.2 and 3p12. We have identified and characterized a new 3p21.3 homozygous deletion in a breast cancer cell line and the primary tumor that overlaps those previously described in small cell lung cancer (SCLC). This homozygous deletion is approximately 220 kb in length and represents a somatically acquired change in the primary breast cancer. Cloning and sequencing of the breakpoint demonstrated that this resulted from an interstitial deletion and precisely pinpoints this deletion within the three SCLC homozygous deletions previously reported. This deletion significantly narrows the minimum common deleted region to 120 kb and is distinct from the previously reported region that suppresses tumor formation of the murine A9 fibrosarcoma cells. These findings suggest that a common homozygous deletion region on 3p21.3 is important in both lung and breast cancers. It is likely that this very well characterized region either contains one tumor suppressor gene common to both tumor types or two closely linked tumor suppressor genes specific for each tumor.

Computerized polymorphic marker identification: experimental validation and a predicted human polymorphism catalog.

A computational system for the prediction of polymorphic loci directly and efficiently from human genomic sequence was developed and verified. A suite of programs, collectively called POMPOUS (polymorphic marker prediction of ubiquitous simple sequences) detects tandem repeats ranging from dinucleotides up to 250 mers, scores them according to predicted level of polymorphism, and designs appropriate flanking primers for PCR amplification. This approach was validated on an approximately 750-kilobase region of human chromosome 3p21.3, involved in lung and breast carcinoma homozygous deletions. Target DNA from 36 paired B lymphoblastoid and lung cancer lines was amplified and allelotyped for 33 loci predicted by POMPOUS to be variable in repeat size. We found that among those 36 predominately Caucasian individuals 22 of the 33 (67%) predicted loci were polymorphic with an average heterozygosity of 0.42. Allele loss in this region was found in 27/36 (75%) of the tumor lines using these markers. POMPOUS provides the genetic researcher with an additional tool for the rapid and efficient identification of polymorphic markers, and through a World Wide Web site, investigators can use POMPOUS to identify polymorphic markers for their research. A catalog of 13,261 potential polymorphic markers and associated primer sets has been created from the analysis of 141,779,504 base pairs of human genomic sequence in GenBank. This data is available on our Web site (pompous.swmed.edu) and will be updated periodically as GenBank is expanded and algorithm accuracy is improved.

Localization of the human vascular endothelial growth factor gene, VEGF, at chromosome 6p12.

Using overlapping cosmids representing the vascular endothelial growth factor (VEGF) locus, the VEGF gene was mapped by fluorescence in situ hybridization to chromosome 6p12. This localization permits linkage analysis and the identification of gene interaction in the region, as well as alterations of the VEGF structure or expression in cancer cells with chromosome abnormalities.