Genetic alterations in the coding region of the bak gene in uterine cervical carcinoma.
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ABSTRACT:
SUBMITTER: Wani KM
PROVIDER: S-EPMC2377111 | biostudies-other | 2003 May
REPOSITORIES: biostudies-other
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Project description:To identify genomic alterations in uterine cervical carcinoma of Indian patients. Cancer of the uterine cervix (CACX) is the fourth most frequent carcinoma among women worldwide. In India, it accounts for approximately 132,000 new cases and 74,000 deaths annually contributing to nearly 1/3rd of the global cervical cancer deaths. Although, several etiological factors such as use of oral contraceptives, precocious marriage, multiparity, smoking etc. are seen to modify the risk of CACX, but infection by high risk human papillomavirus (hrHPV) is thought to be the major cause. Interestingly, long latency period for malignant outcome in only a subset of HPV-infected women indicates involvement of additional chromosomal alterations.Since the first report of changes in chromosomal content of CACX, several genome-wide studies reported frequent chromosomal gain of 3q (3q24–29), 1q (1q22–q23, 1q25.3–q32.1) and 5p (5p12–p13) and loss of 3p (3p12–23), 11q (11q22.3–25) and 4p (4p16.3–p16.1). But no study was done to catalogue the precise genomic alterations in CACX of Indian patients. To the best of our knowledge, for the first time the present study revealed precise chromosomal aberrations with differential frequency in Indian CACX patients (n=11). Among these alterations, frequent (>50%) amplifications of distinct chromosomal loci were as follows: 1p36.11-1p31.1, 1q21.1-1q44, 3q13.13-3q29, 5p15.33-5p12, 8q24.3, 16q22.2, 19q13.13-19q13.2, Xp22.33-Xp11.21 and Xq11.2-Xq12. While recurrent (>35%) loss at chromosomal loci, 2q34-2q37.3, 4p16.3-4p12, 4q21.3, 8p23.3, 8p23.2, 8p11.22, 11q14.1-11q25, 13q13.3-13q14.3, and 19p13.3 were also observed. All CACX patients showed precise amplification of chromosome 3 at coordinates 3q25.2-3q26.1 (chr3:154427429-162796745), 3q26.1-3q26.31 (chr3:162901354-175146595) and 3q26.32-3q29 (chr3:175208719-198094926). Highest (72%) loss of chromosomal loci 11q24.3-11q25 (chr11:128926744-135034169) was seen.
2016-12-27 | GSE76911 | GEO
Project description:Cervical cancer is the third most common cancer worldwide, and the development of new diagnosis, prognostic, and treatment strategies is a major interest for public health. Cisplatin, in combination with external beam irradiation for locally advanced disease, or as monotherapy for recurrent/metastatic disease, has been the cornerstone of treatment for more than two decades. Other investigated cytotoxic therapies include paclitaxel, ifosfamide and topotecan, as single agents or in combination, revealing unsatisfactory results. In recent years, much effort has been made towards evaluating new drugs and developing innovative therapies to treat cervical cancer. Among the most investigated molecular targets are epidermal growth factor receptor and vascular endothelial growth factor (VEGF) signaling pathways, both playing a critical role in cervical cancer development. Studies with bevacizumab or VEGF receptor tyrosine kinase have given encouraging results in terms of clinical efficacy, without adding significant toxicity. A great number of other molecular agents targeting critical pathways in cervical malignant transformation are being evaluated in preclinical and clinical trials, reporting preliminary promising data. In the current review, we discuss novel therapeutic strategies which are being investigated for the treatment of advanced cervical cancer.
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Project description:The purposes of the current study were conducted to explore the relationships among long non-coding RNA gene H19 (LncRNA H19) polymorphisms and clinicopathological characteristics of uterine cervical cancer, and patient prognosis in Taiwan. Five genetic variants of LncRNA H19 rs3024270, rs2839698, rs3741219, rs2107425 and rs217727 were recruited from one hundred and thirty-four patients with invasive cancer, 101 with high-grade cervical intraepithelial neoplasia (CIN) of uterine cervix and 325 controls and their genetic distributions were determined. It indicated no associations of these LncRNA H19 genetic variants with development of cervical cancer. CC/CT in LncRNA H19 rs2839698 exhibited less risk to have pelvic lymph node metastasis [Odds ratio (OR): 0.19, 95% Confidence interval (CI):0.04-0.82, p=0.028)], as compared with TT. Meanwhile, cervical cancer patients with AA/AG in rs3741219 also had less risk to develop pelvic lymph node metastasis (OR: 0.17, 95% CI: 0.05-0.63, p=0.008), large tumor (OR: 0.17, 95% CI: 0.04-0.82, p=0.014) as well as parametrium (OR: 0.26, 95% CI: 0.07-0.95, p=0.045) and vagina invasion (OR: 0.25, 95% CI: 0.07-0.91, p=0.041, as compared to those with GG. However, only positive pelvic lymph node metastasis was related to worse recurrence-free survival and poor overall survival. Conclusively, it indicated no association of LncRNA H19 SNPs with cervical carcinogensis in Taiwanese women. Although genotypes TT in LncRNA H19 rs2839698 and GG in rs3741219 are related to some poor clinicopathological parameters of cervical cancer, only pelvic lymph node status could predict 5 year patient survival significantly.
| S-EPMC6856740 | biostudies-literature
Project description:To our knowledge, no study investigates the association of genetic variant distributions of WW domain-containing oxidoreductase (WWOX) gene with development of invasive cancer, clinicopathologic variables and patient survival in uterine cervical cancer for Taiwanese women. We therefore conducted this study to explore the clinical involvements of WWOX single nucleotide polymorphisms (SNPs) in cervical cancer. One hundred and thirty-one patients with cervical invasive cancer and 93 patients with precancerous lesions as well as 316 control women were consecutively enrolled. The genotypic frequencies of WWOX genetic variants rs73569323, rs383362, rs11545028, rs3764340 and rs12918952 were determined by real-time polymerase chain reaction. The results revealed that only WWOX SNP rs3764340 was associated between patients with cervical invasive cancer and normal controls among 5 WWOX genetic variants. Cervical cancer patients with genotypes GA/AA in WWOX SNP rs12918952 were associated with parametrium invasion and pelvic lymph node metastasis. Univariate analysis found that WWOX SNPs rs73569323 and rs11545028 were associated with patient survival, whereas multivariate analysis revealed CT/TT in rs11545028 was the only genetic variant, which could predict better overall survival, among 5 WWOX SNPs in Taiwan. In conclusion, Taiwanese women with CG/GG in WWOX SNP rs3764340 are susceptible to cervical invasive cancer. Cervical cancer patients with GA/AA in rs12918952 tend to have more risk to develop parametrium invasion and pelvic lymph node metastasis. Among 5 WWOX SNPs, rs11545028 is the only genetic variant associated with patient survival, in which CT/TT could predict better overall survival in Taiwanese women.
| S-EPMC6036151 | biostudies-literature
Project description:BackgroundCancer-associated fibroblasts (CAFs) have been recognized as important contributors to cancer development and progression. However, opposing evidence has been published whether CAFs, in addition to epigenetic, also undergo somatic genetic alterations and whether these changes contribute to carcinogenesis and tumour progression.MethodsWe combined multiparameter DNA flow cytometry, flow-sorting and 6K SNP-arrays to study DNA aneuploidy, % S-phase, loss of heterozygosity (LOH) and copy number alterations (CNAs) in cervical cancer-associated stromal cell fractions (n?=?57) from formalin-fixed, paraffin-embedded (FFPE) samples. Tissue sections were examined for the presence of CAFs. Microsatellite analysis was used to confirm LOH findings.ResultsSmooth muscle actin and vimentin immunohistochemistry verified the presence of CAFs in all cases tested. However, we found no evidence for DNA aneuploidy, somatic genetic alterations in the vimentin-positive stromal cell fractions of any samples, while high frequencies of DNA content abnormalities (43/57) and substantial numbers of CNAs and LOH were identified in the keratin-positive epithelial cell fractions. LOH hot-spots on chromosomes 3p, 4p and 6p found were confirmed by microsatellite analysis.ConclusionFrom our study we conclude that stromal cell fractions from cervical carcinomas are DNA diploid, have a genotype undistinguishable from patient-matched normal tissue and are genetically stable. Using flow cytometry and SNP-arrays, stromal genetic changes do not seem to play a role during cervical carcinogenesis and progression. In addition, the stromal cell fraction of cervical carcinomas can be used as reference allowing large retrospective studies of archival FFPE tissues for which no normal reference tissue is available.
| S-EPMC3223353 | biostudies-literature
Project description:Up to date, no study explores the relationship of single nucleotide polymorphisms (SNPs) of long non-coding RNAs HOTAIR (lncRNAs HOTAIR) with cancer recurrence and patient survival in uterine cervical cancer for Taiwanese women. We therefore designed this study to investigate the clinical roles of lncRNAs HOTAIR SNPs in cervical cancer. One hundred and sixteen patients with cervical invasive cancer and 96 patients with preinvasive lesions as well as 318 control women were consecutively recruited. LncRNAs HOTAIR SNPs rs920778, rs12427129, rs4759314 and rs1899663 were analyzed and their genotypic frequencies were examined by real-time polymerase chain reaction. The results indicated that there were no genotypic differences between patients with cervical neoplasia and normal controls as well as among patients with invasive and invasive cancer, and normal controls. However, genotype GG in lncRNAs HOTAIR SNP rs920778 was demonstrated to be a predictor for poorer cancer recurrence probability [p=0.001, hazard ratio (HR): 7.25, 95% CI: 2.19-23.96]. Furthermore, cervical cancer patients with genotype GG in lncRNAs HOTAIR rs920778 had worse overall survival (p =0.002, HR: 7.22, 95% CI: 2.09-24.92). No significant associations exhibited between lncRNAs HOTAIR SNP rs920778 and clinicopathological parameters. In conclusion, this studied lncRNAs HOTAIR SNPs are not associated with cervical carcinongensis. However, lncRNAs HOTAIR SNP rs920778 may be regarded as an independent predictor of cancer recurrence probability and overall survival in cervical cancer patients.
| S-EPMC6158665 | biostudies-literature
Project description:Cervical cancer (CACX) is the tumor of the uterine cervix and its primary etiological factor is the infection of high risk human papilloma virus (hrHPV), primarily HPV16 and HPV18. CACX is the third most commonly diagnosed cancer and the fourth leading cause of cancer deaths in women worldwide. In India, CACX accounts for approximately 1,22,844 new cases and 67,477 deaths annually. It is evident that Indian women are getting diagnosed at invasive stages of CACX leading to poor prognosis. Here, we tried to understand the change in the expression profile during the development of the tumor starting from HPV-negative normal samples to invasive CACX samples and try to understand the pathogenesis of cervical carcinoma in Indian patients.
2021-05-25 | GSE122697 | GEO
Project description:Cancer-associated fibroblasts (CAFs) have been recognized as important contributors to cancer development and progression. However, opposing evidence has been published whether CAFs, in addition to epigenetic, also undergo somatic genetic alterations and whether these changes contribute to carcinogenesis and tumour progression. We combined multiparameter DNA flow cytometry, flow-sorting and 6K SNP-arrays to study DNA aneuploidy, % S-phase, loss of heterozygosity (LOH) and copy number alterations (CNAs) to study somatic genetic alterations in cervical cancer-associated stromal cell fractions (n = 58) from formalin-fixed, paraffin-embedded (FFPE) samples. Tissue sections were examined for the presence of CAFs. Microsatellite analysis was used to study LOH. By flow cytometry we found no proof for DNA aneuploidy in the vimentin-positive stromal cell fractions of any samples (CV G0G1 population 3.7% +/- 1.2; S-phase 1.4% +/- 1.8). The genotype concordance between the stromal cells and the paired normal endometrium samples was > 99.9%. No evidence for CNAs or LOH was found in the stromal cell fractions. In contrast, high frequencies of DNA content abnormalities (43/57), a significant higher S-phase (14.6% +/- 8.5)(p = 0.0001) and substantial numbers of CNAs and LOH were identified in the keratin-positive epithelial cell fractions (CV G0G1 population 4.1% +/- 1.0). Smooth muscle actin and vimentin immunohistochemistry verified the presence of CAFs in all cases tested. LOH hot-spots on chromosomes 3p, 4p and 6p were confirmed by microsatellite analysis but the stromal cell fractions showed retention of heterozygosity only. From our study we conclude that stromal cell fractions from cervical carcinomas are DNA diploid, have a genotype undistinguishable from patient-matched normal tissue and are genetically stable. Stromal genetic changes do not seem to play a role during cervical carcinogenesis and progression. In addition, the stromal cell fraction of cervical carcinomas can be used as reference allowing large retrospective studies of archival FFPE tissues for which no normal reference tissue is available. Paired experiment, Endometrial (non-tumor) cells vs stromal cells from cervical tumors. Biological replicates: 58 patients. From 5 tumors also the tumor fraction was profiled.
2011-11-08 | E-GEOD-29143 | biostudies-arrayexpress
Project description:Cancer-associated fibroblasts (CAFs) have been recognized as important contributors to cancer development and progression. However, opposing evidence has been published whether CAFs, in addition to epigenetic, also undergo somatic genetic alterations and whether these changes contribute to carcinogenesis and tumour progression. We combined multiparameter DNA flow cytometry, flow-sorting and 6K SNP-arrays to study DNA aneuploidy, % S-phase, loss of heterozygosity (LOH) and copy number alterations (CNAs) to study somatic genetic alterations in cervical cancer-associated stromal cell fractions (n = 58) from formalin-fixed, paraffin-embedded (FFPE) samples. Tissue sections were examined for the presence of CAFs. Microsatellite analysis was used to study LOH. By flow cytometry we found no proof for DNA aneuploidy in the vimentin-positive stromal cell fractions of any samples (CV G0G1 population 3.7% +/- 1.2; S-phase 1.4% +/- 1.8). The genotype concordance between the stromal cells and the paired normal endometrium samples was > 99.9%. No evidence for CNAs or LOH was found in the stromal cell fractions. In contrast, high frequencies of DNA content abnormalities (43/57), a significant higher S-phase (14.6% +/- 8.5)(p = 0.0001) and substantial numbers of CNAs and LOH were identified in the keratin-positive epithelial cell fractions (CV G0G1 population 4.1% +/- 1.0). Smooth muscle actin and vimentin immunohistochemistry verified the presence of CAFs in all cases tested. LOH hot-spots on chromosomes 3p, 4p and 6p were confirmed by microsatellite analysis but the stromal cell fractions showed retention of heterozygosity only. From our study we conclude that stromal cell fractions from cervical carcinomas are DNA diploid, have a genotype undistinguishable from patient-matched normal tissue and are genetically stable. Stromal genetic changes do not seem to play a role during cervical carcinogenesis and progression. In addition, the stromal cell fraction of cervical carcinomas can be used as reference allowing large retrospective studies of archival FFPE tissues for which no normal reference tissue is available.
2011-11-08 | GSE29143 | GEO
Project description:Uterine corpus endometrial carcinoma (UCEC) is one of the most common gynecologic malignancies, but only a few biomarkers have been proven to be effective in clinical practice. Previous studies have demonstrated the important roles of non-coding RNAs (ncRNAs) in diagnosis, prognosis, and therapy selection in UCEC and suggested the significance of integrating molecules at different levels for interpreting the underlying molecular mechanism. In this study, we collected transcriptome data, including long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs), of 570 samples, which were comprised of 537 UCEC samples and 33 normal samples. First, differentially expressed lncRNAs, miRNAs, and mRNAs, which distinguished invasive carcinoma samples from normal samples, were identified, and further analysis showed that cancer- and metabolism-related functions were enriched by these RNAs. Next, an integrated, dysregulated, and scale-free biological network consisting of differentially expressed lncRNAs, miRNAs, and mRNAs was constructed. Protein-coding and ncRNA genes in this network showed potential immune and metabolic functions. A further analysis revealed two clinic-related modules that showed a close correlation with metabolic and immune functions. RNAs in the two modules were functionally validated to be associated with UCEC. The findings of this study demonstrate an important clinical application for improving outcome prediction for UCEC.
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