title: Alterations of RASSF1A in premalignant cervical lesions: clinical and prognostic significance.
abstract: 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.
authors.affiliation: Department of Oncogene Regulation, Chittaranjan National Cancer Institute, Kolkata, West Bengal, India.
authors.forename: Sraboni
authors.initials: S
authors.lastname: Mitra
authors.forename: Dipanjana
authors.initials: D
authors.lastname: Mazumder Indra
authors.forename: Partha S
authors.initials: PS
authors.lastname: Basu
authors.forename: Ranajit K
authors.initials: RK
authors.lastname: Mondal
authors.forename: Anup
authors.initials: A
authors.lastname: Roy
authors.forename: Susanta
authors.initials: S
authors.lastname: Roychoudhury
authors.forename: Chinmay K
authors.initials: CK
authors.lastname: Panda
mesh_terms: D000328:Adult; D015220:Calcium Channels / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000401:mortality / Q000473:pathology; D002584:Cervix Uteri / Q000378:metabolism / Q000473:pathology; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D019175:DNA Methylation; D018450:Disease Progression; D005260:Female; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010298:Parity; D011230:Precancerous Conditions / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000235:genetics* / Q000401:mortality / Q000473:pathology
chemical_list: C480968:CACNA2D2 protein, human; D015220:Calcium Channels; C411762:RASSF1 protein, human; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins