Skip to main content
Top
Published in: Medical Oncology 4/2011

01-12-2011 | Original paper

Allelic loss of 6q25-27, the PARKIN tumor suppressor gene locus, in cervical carcinoma

Authors: S. J. Mehdi, M. S. Alam, S. Batra, M. M. A. Rizvi

Published in: Medical Oncology | Issue 4/2011

Login to get access

Abstract

Studies on loss of heterozygosity have been made for Parkin gene-specific microsatellite markers in malignancies like breast, ovary and lungs, and the results have shown a significant association. However, till date, there is no study with respect to Parkin gene-associated microsatellite markers in cervical cancer. The present study deals with the Parkin gene-associated microsatellite markers and the occurrence of its loss of heterozygosity in patients with human cervical cancer. DNA was isolated from the 105 cervical carcinoma samples and matched control specimens. Polymerase chain reaction was performed using primer specific for two intragenic markers D6S1599 and D6S305 present in Parkin introns 2 and 7, respectively, and one marker (D6S1008) at telomeric end and further electrophoresed on 8% denaturing polyacrylamide gel. Overall, 59 of 105 (56%) samples showed loss of heterozygosity in at least one locus in the region examined. The percentage of loss of heterozygosity for these markers ranged from 25% (D6S1008) to 48% (D6S305). Chi-square test was performed, and loss of heterozygosity was found significantly higher in both the intragenic markers (D6S1599 and D6S305) when compared with the locus at telomeric end (D6S1008) with P < 0.05. These data argue that Parkin is a tumor suppressor gene whose inactivation may play an important role in the carcinoma of uterine cervix.
Literature
1.
2.
go back to reference Hansen MF, Cavenee WK. Genetics of cancer predeposition. Cancer Res. 1987;47:5518–27.PubMed Hansen MF, Cavenee WK. Genetics of cancer predeposition. Cancer Res. 1987;47:5518–27.PubMed
3.
go back to reference Knudson AG. Antioncogenes and human cancer. Proc Natl Acad Sci USA. 1993;23:10914–21.CrossRef Knudson AG. Antioncogenes and human cancer. Proc Natl Acad Sci USA. 1993;23:10914–21.CrossRef
4.
go back to reference Theile M, et al. A defined chromosome 6q fragment (at D6S310) harbors a putative tumor suppressor gene for breast cancer. Oncogene. 1996;13:677–85.PubMed Theile M, et al. A defined chromosome 6q fragment (at D6S310) harbors a putative tumor suppressor gene for breast cancer. Oncogene. 1996;13:677–85.PubMed
5.
go back to reference Bastian BC, LeBoit PE, Hamm H, Brocker EB, Pinkel D. Chromosomal gains and losses in primary cutaneous melanomas detected by comparative genomic hybridization. Cancer Res. 1998;58:2170–5.PubMed Bastian BC, LeBoit PE, Hamm H, Brocker EB, Pinkel D. Chromosomal gains and losses in primary cutaneous melanomas detected by comparative genomic hybridization. Cancer Res. 1998;58:2170–5.PubMed
6.
go back to reference Reutzel D, et al. Genomic imbalances in 61 renal cancers from the proximal tubulus detected by comparative genomic hybridization. Cytogenet Cell Genet. 2001;93:221–7.PubMedCrossRef Reutzel D, et al. Genomic imbalances in 61 renal cancers from the proximal tubulus detected by comparative genomic hybridization. Cytogenet Cell Genet. 2001;93:221–7.PubMedCrossRef
7.
go back to reference Jin C, et al. Characterization of chromosome aberrations in salivary gland tumors by FISH, including multicolor COBRA-FISH. Genes Chromosome Cancer. 2001;30:161–7.CrossRef Jin C, et al. Characterization of chromosome aberrations in salivary gland tumors by FISH, including multicolor COBRA-FISH. Genes Chromosome Cancer. 2001;30:161–7.CrossRef
8.
go back to reference Wan M, et al. Suppression of tumorigenicity in human ovarian cancer cell lines is controlled by a 2 cM fragment in chromosomal region 6q24-q25. Oncogene. 1999;18:1545–51.PubMedCrossRef Wan M, et al. Suppression of tumorigenicity in human ovarian cancer cell lines is controlled by a 2 cM fragment in chromosomal region 6q24-q25. Oncogene. 1999;18:1545–51.PubMedCrossRef
9.
go back to reference Jackson A, et al. Deletion of 6q16-q21 in human lymphoid malignancies: a mapping and deletion analysis. Cancer Res. 2000;60:2775–9.PubMed Jackson A, et al. Deletion of 6q16-q21 in human lymphoid malignancies: a mapping and deletion analysis. Cancer Res. 2000;60:2775–9.PubMed
10.
go back to reference Carvalho B, et al. Allelic gains and losses in distinct regions of chromosome 6 in gastric carcinoma. Cancer Genet Cytogenet. 2001;131(1):54–9.PubMedCrossRef Carvalho B, et al. Allelic gains and losses in distinct regions of chromosome 6 in gastric carcinoma. Cancer Genet Cytogenet. 2001;131(1):54–9.PubMedCrossRef
11.
go back to reference De Souza AT, et al. Frequent loss of heterozygosity on 6q at the mannose 6-phosphate/insulin-like growth factor II receptor locus in human hepatocellular tumors. Oncogene. 1995;10(9):1725–9.PubMed De Souza AT, et al. Frequent loss of heterozygosity on 6q at the mannose 6-phosphate/insulin-like growth factor II receptor locus in human hepatocellular tumors. Oncogene. 1995;10(9):1725–9.PubMed
12.
go back to reference Merlo A, et al. Homozygous deletion on chromosome 9p and loss of heterozygosity on 9q, 6p, and 6q in primary human small cell lung cancer. Cancer Res. 1994;54:2322–6.PubMed Merlo A, et al. Homozygous deletion on chromosome 9p and loss of heterozygosity on 9q, 6p, and 6q in primary human small cell lung cancer. Cancer Res. 1994;54:2322–6.PubMed
13.
go back to reference Visakorpi T, et al. Genetic changes in primary reccurent prostate cancer by comparative genomic hybridization. Cancer Res. 1995;55:342–7.PubMed Visakorpi T, et al. Genetic changes in primary reccurent prostate cancer by comparative genomic hybridization. Cancer Res. 1995;55:342–7.PubMed
14.
go back to reference Tahara H, Smith AP, Gaz RD, Cryns VL, Arnold A. Genomic localization of novel candidate tumor suppressor gene loci in human parathyroid adenomas. Cancer Res. 1996;56:599–605.PubMed Tahara H, Smith AP, Gaz RD, Cryns VL, Arnold A. Genomic localization of novel candidate tumor suppressor gene loci in human parathyroid adenomas. Cancer Res. 1996;56:599–605.PubMed
15.
go back to reference Lemeta S, et al. Loss of heterozygosity at 6q is frequent and concurrent with 3p loss in sporadic and familial capillary hemangioblastomas. J Neuropathol Exp Neurol. 2004;63(10):1072–9.PubMed Lemeta S, et al. Loss of heterozygosity at 6q is frequent and concurrent with 3p loss in sporadic and familial capillary hemangioblastomas. J Neuropathol Exp Neurol. 2004;63(10):1072–9.PubMed
16.
go back to reference Inoue M, et al. Chromosome 6 suffers frequent and multiple aberrations in thymoma. Am J Pathol. 2002;161(4):1507–13.PubMedCrossRef Inoue M, et al. Chromosome 6 suffers frequent and multiple aberrations in thymoma. Am J Pathol. 2002;161(4):1507–13.PubMedCrossRef
17.
go back to reference Mazurenko NN, et al. Genetic alterations at chromosome 6 associated with cervical cancer progression. Mol Biol. 2003;37(3):404–11.CrossRef Mazurenko NN, et al. Genetic alterations at chromosome 6 associated with cervical cancer progression. Mol Biol. 2003;37(3):404–11.CrossRef
18.
go back to reference Sheng ZM, et al. Multiple regions of chromosome 6q affected by loss of heterozygosity in primary human breast carcinomas. Br J Cancer. 1996;73:144–7.PubMedCrossRef Sheng ZM, et al. Multiple regions of chromosome 6q affected by loss of heterozygosity in primary human breast carcinomas. Br J Cancer. 1996;73:144–7.PubMedCrossRef
19.
go back to reference Colitti CV, Rodabaugh KJ, Welch WR, Berkowitz RS, Mok SC. A novel 4 cM minimal deletion unit on chromosome 6q25.1-q25.2 associated with high grade invasive epithelial ovarian carcinoma. Oncogene. 1998;16:555–9.PubMedCrossRef Colitti CV, Rodabaugh KJ, Welch WR, Berkowitz RS, Mok SC. A novel 4 cM minimal deletion unit on chromosome 6q25.1-q25.2 associated with high grade invasive epithelial ovarian carcinoma. Oncogene. 1998;16:555–9.PubMedCrossRef
20.
go back to reference Tibiletti MG, et al. Early involvement of 6q in surface epithelial ovarian tumors. Cancer Res. 1996;56:4493–8.PubMed Tibiletti MG, et al. Early involvement of 6q in surface epithelial ovarian tumors. Cancer Res. 1996;56:4493–8.PubMed
21.
go back to reference Cooke IE, Shelling AN, Le Meuth VG, Charnock ML, Ganesan TS. Allele loss on chromosome arm 6q and fine mapping of the region at 6q27 in epithelial ovarian cancer. Genes Chromosomes Cancer. 1996;15:223–33.PubMedCrossRef Cooke IE, Shelling AN, Le Meuth VG, Charnock ML, Ganesan TS. Allele loss on chromosome arm 6q and fine mapping of the region at 6q27 in epithelial ovarian cancer. Genes Chromosomes Cancer. 1996;15:223–33.PubMedCrossRef
22.
go back to reference Tibiletti MG, et al. Physical map of the D6S149-D6S193 region on chromosome 6Q27 and its involvement in benign surface epithelial ovarian tumours. Oncogene. 1998;16:1639–42.PubMedCrossRef Tibiletti MG, et al. Physical map of the D6S149-D6S193 region on chromosome 6Q27 and its involvement in benign surface epithelial ovarian tumours. Oncogene. 1998;16:1639–42.PubMedCrossRef
23.
go back to reference Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.PubMedCrossRef Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.PubMedCrossRef
24.
go back to reference American Cancer Society. Facts & Figures 2009. American Cancer Society. Facts & Figures 2009.
25.
go back to reference Ferlay J. GLOBOCAN 2002. Cancer Incidence, Mortality and Prevalence Worldwide. IARC 2004; CancerBase No.5, Version 2.0. IARC Press, Lyon. Ferlay J. GLOBOCAN 2002. Cancer Incidence, Mortality and Prevalence Worldwide. IARC 2004; CancerBase No.5, Version 2.0. IARC Press, Lyon.
26.
go back to reference NATIONAL CANCER REGISTRY PROGRAMME. Consolidated Report of Hospital Based Cancer Registries 2001–2003. ICMR, New Delhi; 2007. NATIONAL CANCER REGISTRY PROGRAMME. Consolidated Report of Hospital Based Cancer Registries 2001–2003. ICMR, New Delhi; 2007.
27.
go back to reference Kisseljov F, et al. Instability of chromosome 6 microsatellite repeats in human cervical tumors carrying papillomavirus sequences. Int J Cancer. 1996;69:484–7.PubMedCrossRef Kisseljov F, et al. Instability of chromosome 6 microsatellite repeats in human cervical tumors carrying papillomavirus sequences. Int J Cancer. 1996;69:484–7.PubMedCrossRef
28.
go back to reference Kersemaekers AMF, van de Vijver MJ, Kenter GG, Fleuren GJ. Genetic alterations during the progression of squamous cell carcinomas of the uterine cervix. Genes Chromosomes Cancer. 1999;26:346–54.PubMedCrossRef Kersemaekers AMF, van de Vijver MJ, Kenter GG, Fleuren GJ. Genetic alterations during the progression of squamous cell carcinomas of the uterine cervix. Genes Chromosomes Cancer. 1999;26:346–54.PubMedCrossRef
29.
go back to reference Mazurenko N, et al. High resolution mapping of chromosome 6 deletions in cervical cancer. Oncol Rep. 1999;6:859–63.PubMed Mazurenko N, et al. High resolution mapping of chromosome 6 deletions in cervical cancer. Oncol Rep. 1999;6:859–63.PubMed
30.
go back to reference Chatterjee A, et al. Mapping the sites of putative tumor suppressor genes at 6p25 and 6p21.3 in cervical carcinoma: occurrence of allelic deletions in precancerous lesions. Cancer Res. 2001;61:2119–23.PubMed Chatterjee A, et al. Mapping the sites of putative tumor suppressor genes at 6p25 and 6p21.3 in cervical carcinoma: occurrence of allelic deletions in precancerous lesions. Cancer Res. 2001;61:2119–23.PubMed
31.
go back to reference Mazurenko NN, et al. Genetic changes associated with cervical cancer progression on chromosome 6. Mol Biol. 2003;37:472–81.CrossRef Mazurenko NN, et al. Genetic changes associated with cervical cancer progression on chromosome 6. Mol Biol. 2003;37:472–81.CrossRef
32.
go back to reference Rader JS, Li Y, Huettner PC, Xu Z, Gerhard D. Cervical cancer suppressor gene is within 1 cM on 6p23. Genes Chromos Cancer. 2000;27:373–9.PubMedCrossRef Rader JS, Li Y, Huettner PC, Xu Z, Gerhard D. Cervical cancer suppressor gene is within 1 cM on 6p23. Genes Chromos Cancer. 2000;27:373–9.PubMedCrossRef
33.
go back to reference Chuaqui R, Silva M, Emmert-Buck M. Allelic deletion mapping on chromosome 6q and X chromosome inactivation clonality patterns in cervical intraepithelial neoplasia and invasive carcinoma. Gynecol Oncol. 2001;80:364–71.PubMedCrossRef Chuaqui R, Silva M, Emmert-Buck M. Allelic deletion mapping on chromosome 6q and X chromosome inactivation clonality patterns in cervical intraepithelial neoplasia and invasive carcinoma. Gynecol Oncol. 2001;80:364–71.PubMedCrossRef
34.
go back to reference Cesari R, et al. Parkin, a gene implicated in autosomal recessive juvenile parkinsonism, is a candidate tumor suppressor gene on chromosome 6q25-q27. Proc Natl Acad Sci USA. 2003;100(10):5956–61.PubMedCrossRef Cesari R, et al. Parkin, a gene implicated in autosomal recessive juvenile parkinsonism, is a candidate tumor suppressor gene on chromosome 6q25-q27. Proc Natl Acad Sci USA. 2003;100(10):5956–61.PubMedCrossRef
35.
go back to reference Kitada T, et al. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature. 1998;392:605–8.PubMedCrossRef Kitada T, et al. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature. 1998;392:605–8.PubMedCrossRef
36.
go back to reference West A, et al. Identification and characterization of the human parkin gene promoter. J Neurochem. 2001;78:1146–52.PubMedCrossRef West A, et al. Identification and characterization of the human parkin gene promoter. J Neurochem. 2001;78:1146–52.PubMedCrossRef
37.
go back to reference Denison SR, et al. Genetic alteration in the common fragile site gene PARK2 in ovarian and other cancers. Oncogene. 2003;22:8370–8.PubMedCrossRef Denison SR, et al. Genetic alteration in the common fragile site gene PARK2 in ovarian and other cancers. Oncogene. 2003;22:8370–8.PubMedCrossRef
38.
go back to reference Hattori N, et al. Point mutations (Thr240Arg and Gln311Stop) [correction of Thr240Arg and Ala311Stop] in the Parkin gene. Biochem Biophys Res Commun. 1998;249:754–8.PubMedCrossRef Hattori N, et al. Point mutations (Thr240Arg and Gln311Stop) [correction of Thr240Arg and Ala311Stop] in the Parkin gene. Biochem Biophys Res Commun. 1998;249:754–8.PubMedCrossRef
39.
go back to reference Periquet M, et al. Origin of the mutations in the parkin gene in Europe: exon rearrangements are independent recurrent events, whereas point mutations may result from Founder effects. Am J Hum Genet. 2001;68:617–26.PubMedCrossRef Periquet M, et al. Origin of the mutations in the parkin gene in Europe: exon rearrangements are independent recurrent events, whereas point mutations may result from Founder effects. Am J Hum Genet. 2001;68:617–26.PubMedCrossRef
40.
go back to reference Wang F, et al. Parkin gene alterations in hepatocellular carcinoma. Genes Chromosome Cancer. 2004;40:85–96.CrossRef Wang F, et al. Parkin gene alterations in hepatocellular carcinoma. Genes Chromosome Cancer. 2004;40:85–96.CrossRef
41.
go back to reference Picchio MC, et al. Alterations of the tumor suppressor gene Parkin in non-small cell lung cancer. Clin Cancer Res. 2004;10:2720–4.PubMedCrossRef Picchio MC, et al. Alterations of the tumor suppressor gene Parkin in non-small cell lung cancer. Clin Cancer Res. 2004;10:2720–4.PubMedCrossRef
42.
go back to reference Veeriah S, et al. Somatic mutations of the Parkinson’s disease-associated gene PARK2 in glioblastoma and other human malignancies. Nat Genet. 2010;42(1):77–82.PubMedCrossRef Veeriah S, et al. Somatic mutations of the Parkinson’s disease-associated gene PARK2 in glioblastoma and other human malignancies. Nat Genet. 2010;42(1):77–82.PubMedCrossRef
43.
go back to reference Gunduz E, et al. Loss of heterozygosity at the 9p21-24 region and identification of BRM as a candidate tumor suppressor gene in head and neck squamous cell carcinoma. Cancer Invest. 2009;27(6):661–8.PubMedCrossRef Gunduz E, et al. Loss of heterozygosity at the 9p21-24 region and identification of BRM as a candidate tumor suppressor gene in head and neck squamous cell carcinoma. Cancer Invest. 2009;27(6):661–8.PubMedCrossRef
44.
go back to reference Sambrook J, Russell DW. Molecular cloning: a laboratory manual. 3rd ed. Plainview: Cold Spring Harbor Lab. Press; 2001. Sambrook J, Russell DW. Molecular cloning: a laboratory manual. 3rd ed. Plainview: Cold Spring Harbor Lab. Press; 2001.
45.
go back to reference Yuping X, Lili M, Chengbo H, Jinyi L, Lei X. MSI/LOH and extron expression of the FHIT gene in gastric carcinoma. Front Med China. 2007;1(1):99–103.CrossRef Yuping X, Lili M, Chengbo H, Jinyi L, Lei X. MSI/LOH and extron expression of the FHIT gene in gastric carcinoma. Front Med China. 2007;1(1):99–103.CrossRef
46.
go back to reference Preacher KJ. Calculation for the chi-square test: an interactive calculation tool for chi-square tests of goodness of fit and independence [Computer software]. 2001. Available from http://www.quantpsy.org. Preacher KJ. Calculation for the chi-square test: an interactive calculation tool for chi-square tests of goodness of fit and independence [Computer software]. 2001. Available from http://​www.​quantpsy.​org.
47.
go back to reference Guo T, Sun J. The changes and significance of microsatellite loss of heterozygosity in laryngeal premalignant lesions and squamous cell carcinoma. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2007;21(18):831–3.PubMed Guo T, Sun J. The changes and significance of microsatellite loss of heterozygosity in laryngeal premalignant lesions and squamous cell carcinoma. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2007;21(18):831–3.PubMed
48.
go back to reference West A, et al. Complex relationship between Parkin mutations and Parkinson disease. Am J Med Genet. 2002;114:584–91.PubMedCrossRef West A, et al. Complex relationship between Parkin mutations and Parkinson disease. Am J Med Genet. 2002;114:584–91.PubMedCrossRef
49.
go back to reference Denison SR, Callahan G, Becker NA, Phillips L, Smith DI. Characterization of FRA6E and its potential role in autosomal recessive juvenile parkinsonism and ovarian cancer. Genes Chromosomes Cancer. 2003;38:40–52.PubMedCrossRef Denison SR, Callahan G, Becker NA, Phillips L, Smith DI. Characterization of FRA6E and its potential role in autosomal recessive juvenile parkinsonism and ovarian cancer. Genes Chromosomes Cancer. 2003;38:40–52.PubMedCrossRef
50.
go back to reference Agirre X, et al. Abnormal methylation of the common PARK2 and PACRG promoter is associated with downregulation of gene expression in acute lymphoblastic leukemia and chronic myeloid leukemia. Int J Cancer. 2006;118:1945–53.PubMedCrossRef Agirre X, et al. Abnormal methylation of the common PARK2 and PACRG promoter is associated with downregulation of gene expression in acute lymphoblastic leukemia and chronic myeloid leukemia. Int J Cancer. 2006;118:1945–53.PubMedCrossRef
Metadata
Title
Allelic loss of 6q25-27, the PARKIN tumor suppressor gene locus, in cervical carcinoma
Authors
S. J. Mehdi
M. S. Alam
S. Batra
M. M. A. Rizvi
Publication date
01-12-2011
Publisher
Springer US
Published in
Medical Oncology / Issue 4/2011
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-010-9633-x

Other articles of this Issue 4/2011

Medical Oncology 4/2011 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.