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Alterations of RASSF1A in premalignant cervical lesions: Clinical and prognostic significance
Author(s) -
Mitra Sraboni,
Mazumder Indra Dipanjana,
Basu Partha S.,
Mondal Ranajit K.,
Roy Anup,
Roychoudhury Susanta,
Panda Chinmay K.
Publication year - 2012
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20837
Subject(s) - biology , methylation , cervical intraepithelial neoplasia , carcinogenesis , gene , cancer research , dna methylation , tumor progression , carcinoma , stage (stratigraphy) , gene expression , pathology , cancer , genetics , cervical cancer , medicine , paleontology
This study aimed to understand the importance of RASSF1A and CACNA2D2 , located in chromosomal 3p21.31 region, in the development of uterine cervical carcinoma (CACX). To this end, firstly the expression (RNA) profiles of RASSF1A and CACNA2D2 were screened in primary cervical carcinoma (CACX) samples which indicated highly reduced expression for both genes. Thereafter alterations (deletion/methylation) of these genes were analyzed in 23 cervical intraepithelial neoplasia (CIN) and 110 CACX samples. In CIN, deletion was observed only for RASSF1A (26%), whereas methylation was in the following order: RASSF1A (35%) > CACNA2D2 (9%). However, in CACX their deletion frequencies were the same (50%) and methylation frequencies were comparable RASSF1A (33%), CACNA2D2 (27%). The reduced expression and molecular alterations of these genes were concordant. Overall alterations of RASSF1A showed association with CIN lesions and CACNA2D2 with disease progression from CIN → stage I/II. Interestingly, alterations of these genes showed significant association in CACX suggesting possible functional synergism during tumor progression. Alterations of RASSF1A and CACNA2D2 predicted poor prognosis for the patients. Moreover, RASSF1A alterations along with multiparity (≥5 yr) and early sexual debut (<19 yr) were determinants of worse prognosis. Our data suggests the association of RASSF1A and CACNA2D2 in cervical carcinogenesis and its importance in early diagnosis and prognosis of the tumor. © 2011 Wiley Periodicals, Inc.