Study on relationship between human papilloma virus,telomerase gene and chromosome 3 number with cervical lesions / 国际检验医学杂志

Objective To explore the relationship between the expression of human telomerase RNA component (TERC) gene , human papilloma virus (HPV) infection and mutation of chromosome 3 number with cervical lesions .Methods 81 women received the treatment in the Gynecology Department of the Second Affiliated Hospital of Kunming Medical University from June 2008 to February 2009 ,including the healthy group(normal pathological examination ,20 cases) ,CIN1 group(28 cases) ,CIN2 group(12 ca‐ses) ,CIN3 group(9 cases) and cervical cancer group(12 cases) .The TERC gene expression in uterine epithelial exfoliated cells was detected by using the fluorescence in situ hybridization (FISH) method ,meanwhile the HPV infection was detected by using the real time fluorescence quantitative polymerase chain reaction (FQPCR) technology .The correlation between cervical cancer with TERC gene and HPV was analyzed .At the same time the number of chromosome 3 mutations in 81 cases was recorded .Results In the cervical lesion detection ,the detection positive rate had no statistical difference between the TERC gene detection and HPV detec ‐tion (P> 0 .05) ,their positive rates in the CIN 1 ,CIN2 ,CIN3 and cervical cancer groups were significantly higher than that in the healthy group (P 0 .05) , while between the CIN3 group and the cervical cancer group had statistical significance (P< 0 .05) ,the higher the malignant degree , the higher the positive rate .The abnormal mutation rate of chromosome 3 number was 0% in the healthy group and the CIN1 group ,16 .7% in the CIN2 group ,66 .7% in the CIN3 group and 100 .0% in the cervical cancer group ,the positive rate in the CIN3 group and the cervical cancer group was significantly higher than that in the healthy group ,CIN1 group and CIN2 group ,the differ‐ences were statistically significant (P< 0 .05) .Conclusion The TERC abnormal gene expression ,high risk HPV infection and mutation of chromosome 3 number could play an important synergistic effect during the process of occurrence and progression of cervical cancer .

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.

Clinical characterization of a Korean case with 3p25 deletion

Chromosome 3 (3p) deletion syndrome is a rare genomic disorder caused by a deletion at the terminal end of the short arm of chromosome 3. The primary characteristics of the syndrome are delayed development, dysmorphic features, and several other congenital anomalies. Here, we describe the case of a 2-year-old Korean girl with typical features of 3p deletion syndrome, including dysmorphic facial features, low birth weight, developmental delay, growth and cognitive retardation, and congenital heart disease. This case represents the first report of 3p deletion syndrome in Korea. Although phenotypes can be variable among patients, a clinically recognizable pattern has been described for this genetic defect, and our report helps to identify other cases with 3p deletion syndrome from a clinical and genetic perspective.

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.

Chromosome 3p tumour suppressor genes and clear cell renal cell carcinoma / 国际肿瘤学杂志

The abnormal changes of tumor suppressor genes such as deletion mutant,transcription inactivation or silence on human chromosome 3p (pter) are considered as a key step which is closely related to the tumorigenesis of several kinds of cancers,especially clear cell renal cell carcinoma,one kind of renal cancer.And on this basis,it has been confirmed that the deletion and downregulation of multiple 3p genes such as VHL,RASSF1A,SEMA3B,SETD2,PBRM1,NPRL2 and so on,play a vital important role in the tumorigenesis and development of clear cell renal cell carcinoma.And they provide a further way to explain the molecular mechanism of the tumorigenesis of kidney cancer.However,when the regulatory pathway and mechanism research of some genes are known to us,the other genes,especially those newly founded,which are still not clear and need to be further investigated.

A Case of Addition of Chromosome 3 associated with Multiple Anomalies

Chromosomal anomalies are associated with various congenital malformations and impaired development. The addition or duplication of chromosome 3 is a very rare chromosomal anomaly, in comparison to the deletion of chromosome 3. To date, only one case of the duplication of chromosome 3p has been reported, but an addition or duplication of chromosome 3p was not reported in Korea. We experienced a case of the addition of chromosome 3 in a male newborn infant who had suffered from multiple anomalies and congenital heart disease, atrioventricular septal defects and coarctation of the aorta. The karyotype of this patient was 46, XY, add(3)(p25). We report the case with the review of the associated literatures.

Hematologic and Clinical Features of 3q21q26 Syndrome: Extremely Poor Prognosis and Association with Central Diabetes Insipidus / 대한진단검사의학회지

BACKGROUND: 3q21q26 syndrome includes chromosomal abnormalities of inv(3)(q21q26), t(3;3) (q21;q26), and ins(3;3)(q26;q21q26). It causes hematological diseases by the leukemogenic mechanism that the enhancer of ribophorin I gene in 3q21 induces the transcription of ecotropic viral integration site-1 gene in 3q26. Recently, it has been proposed that the 3q21q26 syndrome may be preceded by diabetes insipidus (DI), particularly when combined with monosomy 7, and is a unique disease entity. METHODS: From May 2001 to June 2006, a total of 5 patients with hematologic malignancy were found to have 3q21q26 syndrome and monosomy 7. Laboratory findings, clinical data, and association with DI were investigated. RESULTS: The rearrangement type of 3q21q26 was inv(3)(q21q26) in four patients and t(3;3)(q21; q26) in one. These patients' French American British types were AML M1, M2, M4 and M7, showing evident dysmegakaryopoiesis. Aberrant antigenic expressions of CD7 and CD56 were observed. The platelet count was relatively high as AML. All the five patients were refractory or in early relapse. Patient 5 was diagnosed with AML M7 20 days after being diagnosed with DI. While DI was well controlled with oral desmopressin, leukemia was refractory to chemotherapy. CONCLUSIONS: This study supports the recent opinion that 3q21q26 syndrome with monosomy 7 combined with DI is a disease of unique characteristics. In the relation between DI and monosomy 7 or 3q21q26 syndrome, there has been no explanation about how acquired abnormality of hematopoietic cells affects production of DDAVP by neurohormonal cells in hypothalamus. The mechanism needs further study, and this research should contribute to the understanding of genetic roles in leukemia appearing in different forms.

A Case of Short Arm Deletion and Long Arm Duplication at Chromosome 3 / 소아과

The long arm duplication of chromosome 3 was reported for the first time in 1966 by Falek et al., and Hirschhorn et al. came to identify the duplication of 3q21--> qter region in 1973. In most cases of duplication 3q syndrome patients, pure duplication of 3qter is believed to be rare and is often reported accompanied with deletion of another segment of the chromosome. Approximately 75 percent of parents of the patient in the meantime have been demonstrated to have unbalanced translocations or inversions of the chromosome. Partial deletion of the distal part of the short arm of chromosome 3 was first reported by Verjaal and De Nef in 1978 and terminal deletion of chromosome 3 (3p25- qter) has been observed in most cases. In karyotyping of chromosomes of immature infants showing the manifestations of flat occiputs, low set ears, hypertelorism, broad nasal roots, thin lips, web necks, hypotonia, hypertrichosis skin, cryptorchidism etc, we experienced a case diagnosed as 46, XY, rec (3) dup (3) (q21) del (3) (p25) inv (3) (p25q21).

3q Chromosomal Abnormalities Associated with Dysmegakaryopoiesis in Acute Leukemias / 대한임상병리학회지

BACKGROUND: Abnormalities of chromosome 3q21-26 in patients with hematologic malignancies have been suggested to be associated with normal or elevated platelet counts and abnormal megakaryopoiesis. However, the relationship and pathogenic mechanisms are not yet clear. Therefore, we have attempted to clarify the relation of the chromosome 3q abnormalities with dysmegakaryopoiesis in 23 leukemia patients. METHODS: We reviewed retrospectively bone marrow studies, cytogenetic analyses and clinical records of 229 patients with leukemia (AML, ALL or CML in blastic crisis) between 1995 and 1999 with the emphasis on thrombocytopenia, chromosome 3q abnormalities, and dysmegakaryopoiesis in bone marrow. RESULTS: Among 229 leukemia patients, 9 patients (3.9%) had chromosome 3q abnormalities, 11 (4.8%) had dysmegakaryopoiesis and 13 (5.7%) showed normal to increased platelet counts. The platelet count of 9 patients with chromosome 3q abnormalities ranged from 7x109/L to 1623x109/L and 6 of them had decreased numbers of platelets and megakaryocytes, and two patients had dysmegakaryopoiesis. Among them, three patients had an increased number of megakaryocytes with dysmegakaryopoiesis and showed t (2; 3)(q31; q25) or inv (3)(q21q26). They showed a good response to standard chemotherapy. 8 of 10 patients, but neither thrombocytopenia nor chromosome 3q abnormalities, had normal or an increased number of megakaryocytes. CONCLUSIONS: No major prognostic influence was found due to the presence of large numbers of dysplastic megakaryocytes and normal to increased platelet counts in acute leukemia and seemingly were not uniquely associated with changes involving chromosome 3q and abnormalities of 3q21 and 3q26 associated with dysplastic megakaryocytes.

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.