Alterations of RASSF1A in premalignant cervical lesions: Clinical and prognostic significance

• Published in: Molecular carcinogenesis 2012-09, Vol.51 (9), p.723-733
• Main Authors: Mitra, Sraboni, Mazumder (Indra), Dipanjana, Basu, Partha S., Mondal, Ranajit K., Roy, Anup, Roychoudhury, Susanta, Panda, Chinmay K.
• Format: Article
• Language: English
• Subjects: Adult; CACNA2D2; Calcium Channels - genetics; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - mortality; Carcinoma, Squamous Cell - pathology; Cervical cancer; Cervical Intraepithelial Neoplasia - genetics; Cervical Intraepithelial Neoplasia - mortality; Cervical Intraepithelial Neoplasia - pathology; Cervix Uteri - metabolism; Cervix Uteri - pathology; Chromosomes, Human, Pair 3 - genetics; CIN; deletion; Disease Progression; DNA Methylation; Female; Gene Deletion; Gene Expression Regulation, Neoplastic; Genetics; Human papillomavirus; Humans; methylation; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Oncology; Parity; Precancerous Conditions - genetics; Precancerous Conditions - mortality; Precancerous Conditions - pathology; Prognosis; Promoter Regions, Genetic - genetics; RASSF1A; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA; RNA, Messenger - genetics; Survival Rate; Tumor Suppressor Proteins - genetics; uterine cervical carcinoma; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - mortality; Uterine Cervical Neoplasms - pathology
• ISSN: 0899-1987; 1098-2744
• DOI: 10.1002/mc.20837

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 (