Molecular Biomarkers for Early Detection and Prevention of Ovarian Cancer—A Gateway for Good Prognosis: A Narrative Review

Geetanjali Yadav, Minakshi Vashisht, Vipul Yadav, Radhey Shyam

Abstract


Gynecological cancers are one of the most lethal and deadliest cancers in the world. In India, the prevalence of ovarian cancer accounts for 2.5% to 3%. Despite the availability of improved treatment option along with improved technology, the survival rate of ovarian cancer in the early‑stage and the advanced stage is poor. Therefore, due to the heterogeneity of ovarian cancer, to detect it at an early stage and to prevent further mortality turns out to be a big challenge. Researchers are still in the process to identify any single biomarker with good sensitivity and specificity. Various traditional and serum approaches to identify ovarian cancer have been successful in the early stages. The invention of molecular biomarkers such as the use of genomic profiling, DNA methylation, and other approaches have proven to be of higher sensitivity and specificity, which overall affects the prognosis of ovarian cancer. With the use of whole‑genome analysis, the detection of possible location of critical tumor suppressor gene (TSGs) in the paired region of chromosomes has been identified, which are associated with BRCA1 and BRCA2 which further makes these novel molecular biomarkers as potential biomarkers. Moreover, studies are required to assess the combined use of traditional, molecular biomarkers that might be useful for enhanced sensitivity and specificity for early detection and prevention of ovarian cancer in early stages which will lead to reduced mortality and good prognosis

Keywords


Molecular biomarkers; ovarian cancer; preventive medicine

Full Text:

PDF

References


Sreeja S, Ayala T, Heejin L, Shihong L, Shifang Z, Andre G,

et al. Early detection biomarkers for ovarian cancer. J Oncol

;14:12‑26.

Cho KR, Shih IeM. Ovarian cancer. Ann Rev Pathol

;4:287‑313.

Kiechle M, Jacobsen A, Schwarz‑Boeger U. Comparative

genomic hybridization detects genetic imbalances in primary

ovarian carcinomas as correlated with grade of differentiation.

Cancer 2001;9:1534‑40.

Rubin SC. Chemoprevention of hereditary ovarian cancer.

N Engl J Med 1998;339:469‑71.

Ben David Y, Chetrit A, Hirsh‑Yechezkel G, Friedman E, Beck BD,

Beller U, et al. Effect of BRCA mutations on the length of survival

in epithelial ovarian tumors. J Clin Oncol 2002;20:463‑6.

Prat J, Ribe A, Gallardo A. Hereditary ovarian cancer. Hum

Pathol 2005;36:861‑70.

Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics,

CA Cancer J Clin 2005;55:74‑108.

Carroll JC, Cremin C, Allanson J, Blaine SM, Dorman H,

Gibbons CA, et al. Hereditary breast and ovarian cancers. Can

Fam Physician 2008;54:1691‑2.

Russo A, Calò V, Bruno L, Rizzo S, Bazan V, Di Fede G.

Hereditary ovarian cancer. Crit Rev Oncol Hematol

;69:28‑44.

Agnantis NJ, Fatouros M, Arampatzis I, Briasoulis E,

Ignatiadou EV, Paraskevaidis E, et al. Carcinogenesis of breast

cancer: Advances and applications. Gastric Breast Cancer

;3:13‑22.

Stavropoulou AV, Fostira F, Pertesi M, Tsitlaidou M,

Voutsinas GE, Triantafyllidou O, et al. Prevalence of BRCA1

mutations in familial and sporadic greek ovarian cancer cases.

PLoS One 2013;8:e58182.

de Jong MM, Nolte IM, te Meerman GJ, van der Graaf WT,

Oosterwijk JC, Kleibeuker JH, et al. Genes other than BRCA1

and BRCA2 involved in breast cancer susceptibility. J Med

Genet 2002;39:225‑42.

UCSC Genome Bioinformatics Group. Available from: http://

genome.ucsc.edu/cgi‑bin/hgGateway. [Last accessed on

Jan 12].

Shaw PA, McLaughlin JR, Zweemer RP, Narod SA,

Risch H, Verheijen RH, et al. Histopathologic features of

genetically determined ovarian cancer. Int J Gynecol Pathol

;21:407‑11.

Foster KA, Harrington P, Kerr J, Russell P, DiCioccio RA,

Scott IV, et al. Somatic and germline mutations of the BRCA2

gene in sporadic ovarian cancer. Cancer Res 1996;56:3622‑5.

Ensembl Genome Browser. Available from: http://www.ensembl.

org/index.html.

Liede A, Malik IA, Aziz Z, Rios Pd Pde L, Kwan E, Narod SA.

Contribution of BRCA1 and BRCA2 mutations to breast and

ovarian cancer in Pakistan. Am J Hum Genet 2002;71:595‑606.

McCoy ML, Mueller CR, Roskelley CD. The role of the breast

cancer susceptibility gene 1 (BRCA1) in sporadic epithelial

ovarian cancer. Reprod Biol Endocrinol 2003;1:72‑6.

De Leeneer K, Coene I, Crombez B, Simkens J,

Van den Broecke R, Bols A, et al. Prevalence of BRCA1/2

mutations in sporadic breast/ovarian cancer patients and

identification of a novel de novo BRCA1 mutation in a patient

diagnosed with late onset breast and ovarian cancer: Implications

for genetic testing. Breast Cancer Res Treat 2012;132:87‑95.

Brozek I, Ochman K, Debniak J, Morzuch L, Ratajska M,

Stepnowska M, et al. High frequency of BRCA1/2 germline

mutations in consecutive ovarian cancer patients in Poland.

Gynecol Oncol 2008;108:433‑7.

Smirnova TY, Pospekhova NI, Lyubchenko LN, Tjulandin SA,

Gar’kavtseva RF, Ginter EK, et al. High incidence of mutations

in BRCA1 and BRCA2 genes in ovarian cancer. Bull Exp Biol

Med 2007;144:83‑5.

Pohlreich P, Zikan M, Stribrna J, Kleibl Z, Janatova M, Kotlas J,

et al. High proportion of recurrent germline mutations in the BRCA1 gene in breast and ovarian cancer patients from the

Prague area. Breast Cancer Res 2005;7:R728‑36.

Meindl A, Hellebrand H, Wiek C, Erven V, Wappenschmidt B,

Niederacher D, et al. Germline mutations in breast and ovarian

cancer pedigrees establish RAD51C as a human cancer

susceptibility gene. Nat Genet 2010;42:410‑4.

Dosanjh MK, Collins DW, Fan W, Lennon GG, Albala JS,

Shen Z, et al. Isolation and characterization of RAD51C, a new

human member of the RAD51 family of related genes. Nucleic

Acids Res 1998;26:1179‑84.

Takata M, Sasaki MS, Tachiiri S, Fukushima T, Sonoda E,

Schild D, et al. Chromosome instability and defective

recombinational repair in knockout mutants of the five Rad51

paralogs. Mol Cell Biol 2001;21:2858‑66.

Vaz F, Hanenberg H, Schuster B, Barker K, Wiek C, Erven V,

et al. Mutation of the RAD51C gene in a fanconi anemia‑like

disorder. Nat Genet 2008;42:406‑9.

Feinberg, AP, Vogelstein, B. Hypomethylation of ras oncogenes

in primary human cancers. Biochem Biophys Res Commun

;111:47‑54.

Savitsky K, Bar‑Shira A, Gilad S, Rotman G, Ziv Y, Vanagaite L,

et al. A single ataxia telangiectasia gene with a product similar

to PI‑3 kinase. Science 1995;268:1749‑53.

Zhao S, Weng YC, Yuan SS, Lin YT, Hsu HC, Lin SC, et al.

Functional link between ataxia‑telangiectasia and Nijmegen

breakage syndrome gene products [see comments]. Nature

;405:473‑7.

Shiloh Y. Ataxia‑telangiectasia and the Nijmegen breakage

syndrome: Related disorders but genes apart. Annu Rev Genet

;31:635‑62.

Greenblatt MS, Bennett WP, Hollstein M, Harris CC. Mutations

in the p53 tumor suppressor gene: Clues to cancer etiology and

molecular pathogenesis. Cancer Res 1994;54:4955‑78.

Russell SE, Hickey GI, Lowry WS, White P, Atkinson RJ.

Allele loss from chromosome 17 in ovarian cancer. Oncogene

;5:1581‑3.

Annual Report on the Treatment of Gynecologic Cancer. In:

Kottmeier HL, editor. International Federation of Gynecologists

and Obstetricians Stockholm, Sweden 1979:17.

Serov SF, Scully RE. Histological typing of ovarian tumors.

In: International Histological Classification of Tumors, No. 9.

Geneva: World Health Organization; 1973.

Wade‑Evans A, Jenkins JR. Precise epitope mapping of the

murine transformation‑associated protein, p53. EMBO J

;4:699‑706.

Banks L, Matlashewski G, Crawford L. Isolation of

human‑p53‑specific monoclonal antibodies and their use

in the studies of human p53 expression. Eur J Biochem

;159:529‑34.

Cvetkovic D, Pisarcik D, Lee C, Hamilton TC, Abdollahi A.

Altered expression and loss of heterozygosity of the LOT1 gene

in ovarian cancer. J Oncol 2004;95:449‑55.

Shin DS, Pellegrini L, Daniels DS, Yelent B, Craig L, Bates D,

et al. Full‑length archaeal RAD51 structure and mutants:

Mechanisms for RAD51 assembly and control by BRCA2.

EMBO J 2003;22:4566‑76.

Weiss MM, Hermsen MA, Meijer GA, van Grieken NC,

Baak JP, Kuipers EJ, et al. Comparative genomic hybridization.

Mol Pathol 1999;52:243‑51.

Patael‑Karasik Y, Daniely M, Gotlieb WH, Ben‑Baruch G,

Schiby J, Barakai G, et al. Comparative genomic hybridization

in inherited and sporadic ovarian tumors in Israel. Cancer Genet

Cytogenet 2000;121:26‑32.

Losi L, Fonda S, Saponaro S, Chelbi ST, Lancellotti C,

Gozzi G, et al. Distinct DNA methylation profiles in ovarian

tumors: Opportunities for novel biomarkers. Int J Mol Sci

;19:E1559.

Imataka G, Arisaka O. Chromosome analysis using spectral

karyotyping (SKY). Cell Biochem Biophys 2012;62:13‑7.

Senturk E, Cohen S, Dottino PR, Martignetti JA. A critical

re‑appraisal of BRCA1 methylation studies in ovarian cancer.

Gynecol Oncol 2010;119:376‑83.

Feinberg AP, Vogelstein B. Hypomethylation distinguishes genes

of some human cancers from their normal counterparts. Nature

;301:89‑92.