A Study on CpG Island Methylator Phenotype involving Tumor Suppressor Genes on Chromosome 3p in Gastric Cancer / 胃肠病学

Background:CpG island methylator phenotype(CIMP)involving tumor suppressor gene( TSG)on short arm of chromosome 3(chromosome 3p)has been found in various types of cancers. However,its correlation with gastric cancer has not been clarified. Aims:To study the clinical significance of CIMP involving TSG on chromosome 3p in gastric cancer. Methods:Methylation specific PCR(MSP)was used to examine methylation profiles for hOGG1,VHL,RAR-B, hMLH1,SEMA3B,RASSF1A,BLU and FHIT harbored in chromosome 3p in 100 gastric cancer and paired paracancerous tissues. High CIMP( CIMP-H)was referred for those samples having four or more synchronously methylated genes. Relationship between CIMP-H and clinicopathological characteristics in gastric cancer was analyzed. Results:Positive methylation rates of VHL(P = 0. 030),hMLH1(P 0. 05). Conclusions:CIMP on chromosome 3p may occur in early stage of oncogenesis of gastric cancer,and influencing tumor differentiation and lymph node metastasis.

Familial Study of Paracentric Inversion in Chromosome 3p.

Aims: To describe the familial occurrence of paracentric inversion of chromosome 3. Presentation of Cases: Patient 1: Female, Caucasian, born in Southeast of Brazil, 7 years old. Born at term and asphyxia. Developmental delay; aggressive behavior and tendency toward isolation. Prominent forehead, discrete epicanthal folds, down-slanting palpebral fissures, long philtrum and hypermobility of the four limbs. Karyotype: 46,XX,inv(3)(p13p25). Patient 2: Female, Caucasian, born in Northeast of Brazil, 3 years old. Born prematurely by cesarean section, pelvic presentation and asphyxia. Severe developmental delay. Microcephaly, bilateral convergent strabismus, epicanthal folds, wide nasal bridge, micrognathia, high arched palate and nasolabial hemangioma, low set ears, hypoplastic nipples, nucal café-au-lait spots, deep plantar fold. Dysgenesis of the corpus callosum. Karyotype: 46,XX,inv(3)(p13p25). Patient 3: Male, Caucasian, born in Southeast of Brazil, 5 years. Born at term, by cesarean section, cephalic presentation. Developmental delay and flexor spasms. Dolichocephalic skull, prominent forehead, ocular hypertelorism, epicanthal folds, disproportioned and low set ears, single palmary crease in the right hand, large and elongated thumbs, hypotonia, and recurrent acute otitis. Karyotype: 46,XY,inv(3)(p13p25). Discussion: Patients presented developmental delay and dysmorphic features, but the relatives that presented the same inversion were asymptomatic. Carriers seem to have a normal reproductive fitness, without differences between males and females. Conclusion: The chromosomal rearrangements, especially balanced chromosomal alterations provide an opportunity to broaden the understanding of the structure and functional organization of chromosomes and to offer better genetic counseling for the families.

Molecular Genetic Investigation of Sporadic Renal Cell Carcinoma: Analysis of Allele Loss on Chromosome 3p / 대한비뇨기과학회지

PURPOSE: Renal cell carcinoma has been characterized by an abnormality on the short arm of chromosome 3, which suggests the presence of a tumor suppressor gene at this location. The aim of study was to investigate the role of tumor suppressor genes on the short arm of chromosome 3 in the mechanism of tumorigenesis in sporadic renal cell carcinoma. MATERIALS AND METHODS: The DNA from normal and tumor tissue from 48cases with renal cell carcinoma was analyzed for allele loss on chromosome 3p by polymerase chain reaction using microsatellite marker. RESULTS: A total of 37 of 48 informative tumors(77%) showed loss of heteroxygosity(LOH) at one or more loci. Detailed analysis of the pattern of LOH on the chromosome 3p suggested that mutations of other genes in chromosome 3p13-p24, in addition to VHL gens in chromosome 3p25, are required for malignant tumor growth. There was the statistically significant correlation between the extent of LOH and cancer cell type(clear vs. others)(p=value 0.048, Fisher's exact test). A total of 26 of 37 clear cell types(70%)revealed LOH on chromosome 3p, but all of 11 non clear cell types including 2 granular cell types, 3 chromophobe types, 1 sarcomatoid cell type and 5 mixed cell types showed LOH. There was no correlation between LOH and other clinico-pathological factors including patients age, sex, symptom, tumor size, stage of disease and tumor cell grade. CONCLUSIONS: Our data suggest that, in addition to VHL gene, at least one tumor suppressor gene for the genesis of sporadic remal cell carcinoma exists on the short arm of chromosome 3.

Expression of the FHIT gene Located in Chromosome 3p14.2 in Human Lung Cancer Cell Lines / 결핵

BACKGROUND: The 3p deletions has been shown to be the most frequent alteration in lung cancers, strongly suggesting the presence of at least one tumor suppressor gene in this chromosomal region. However, no solid candidate for the tumor suppressor gene(s) on 3p has as yet been identified. Recent attention has focused on a candidate 3p14.2 tumor suppressor gene, FHIT, which is located in a .region that is homozygously deleted in multiple tumor cell lines and disrupted by the hereditary renal cell carcinoma t(3;8) chromosomal translocation breakpoint FHIT also spans FRA3B, the most common fragile sites in the human genome. In the present study, we have analyzed expression of the FHIT gene in lung cancer cell lines. METHODS: RNA from 21 lung cancer cell lines (16 NSCLC, 5 SCLC) were extracted using standard procedures. Random-primed, first strand CDNAS were synthesized from total RNA and PCR amplication of coding exons 5 to 9 was performed. The RT-PCR products were electrophoresed in 1.5% ethidium bromide-stained agarose gels. RESULTS: 12 of 21(57%) lung cancer cell lines exhibited absent or aberrant FHIT expression [7 of 16(44%) of non-small cell lung cancer and 5 of 5(100%) of small cell lung cancer cell lines]. CONCLUSION: The result shows that abnormal transcription of the FHIT gene is common in human lung cancer cell lines, especially in small cell lung cancer.