Publications (7)18.13 Total impact
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Article: Frequent deletion and methylation in SH3GL2 and CDKN2A loci are associated with early- and late-onset breast carcinoma.
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ABSTRACT: This study attempts to understand the association of candidate tumour suppressor genes SH3GL2, CDKN2A (p16-p14) and CDKN2B (p15) in development of early-onset (group A) and late-onset (group B) breast carcinoma (BC). Deletion, methylation, and mutation of the candidate tumour suppressor genes (TSGs) were analysed in 47 group A and 59 group B samples. Immunohistochemical analysis was used to identify the expression status of SH3GL2 and p16. Clinicopathological correlation of the alterations was analysed by the chi-square and log-rank tests. Higher frequency of overall alterations (46-62%) in SH3GL2 and p16-p14 than p15 (22-26%) indicated their importance in BC. Deletion frequencies were in the following order: group A: p14 (43%) > p16 (42%) > SH3GL2 (38%) > p15 (33%) and group B: p14 (36%) > p16 (33%) > SH3GL2 (31%) > p15 (14%) while, methylation frequencies were: group A: SH3GL2 (34%) > p16 (28%) > p14 (26%) > p15 (15%) and group B: SH3GL2 (36%) > p16 (31%) > p14 (29%) > p15 (15%). Infrequent mutation was observed only in CDKN2A common exon-2. Immunohistochemical analysis showed significant association between expression of SH3GL2 and p16 with their deletion (P = 0.01 and 0.02, respectively) and methylation status (P = 0.007 and 0.01, respectively). In group A, overall alterations of SH3GL2 showed significant association with CDKN2A locus with significant prognostic implications, whereas CDKN2A and CDKN2B loci were associated in both groups. The molecular mechanisms involving CDKN2A inactivation seem to follow similar pathway in the pathogenesis of both age groups of BC while significant association of SH3GL2 with CDKN2A might play a synergistic role in the development of group A.Annals of Surgical Oncology 05/2008; 15(4):1070-80. · 4.17 Impact Factor -
Article: Deletion in chromosome 11 and Bcl-1/Cyclin D1 alterations are independently associated with the development of uterine cervical carcinoma.
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ABSTRACT: The aim of this study was to understand whether there is any association between specific deleted regions in chromosome 11 (chr.11) and alteration (amplification/rearrangement) of Bcl-1/Cyclin D1 locus, located at 11q13, in uterine cervical carcinoma (CA-CX). The deletion mapping of chr.11 was studied using 17 highly polymorphic microsatellite markers in 65 primary uterine cervical lesions. The Bcl-1/Cyclin D1 alterations were analyzed by Southern blot and/or polymerase chain reaction (PCR) method in respective cervical lesions. Chr.11 deletion was found to be significantly associated with progression of CA-CX. High frequency (48-65%) of deletion was found in 11p15.5 (D1), 11q22.3-23.1(D2), and 11q23.3-24.1(D3) regions and significant association was seen among deletions in D2 and D3 regions. Bcl-1/Cyclin D1 locus alteration was observed in overall 27% cervical lesions. Co-amplification of Bcl-1/Cyclin D1 locus was seen in 10% samples. However, no association was found between the deleted regions and Bcl-1/Cyclin D1 locus alterations. Our study suggests that there is no co-operativity between the deleted regions (D1- D3) in chr.11 and Bcl-1/Cyclin D1 alterations, but these alterations may provide cumulative effect in progression of the tumor. The D1-D3 regions may harbor candidate tumor suppressor gene(s) (TSGs) associated with the development of CA-CX.Journal of Cancer Research and Clinical Oncology 07/2005; 131(6):395-406. · 2.56 Impact Factor -
Article: Differential association of BRCA1 and BRCA2 genes with some breast cancer-associated genes in early and late onset breast tumors.
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ABSTRACT: Accumulating evidence indicating more aggressive features of breast carcinoma (BC) in young women than their older counterparts have raised the question of whether these differences are present at the genetic level. For this purpose, we performed a comparative analysis of the frequency of deletions of BRCA1, BRCA2, BRCAX, TP53, ATM, and RB1 and amplification of Cyclin D1 and also studied the interrelation and prognostic significance of these genetic alterations in 30 early onset (< or =40 years) and 33 late onset (>40 years) cases of BC. These gene alterations were also studied in 11 other types of breast lesions. A differential pattern of alterations (deletion/amplification) was observed in the two age groups, with the sequence in younger women being BRCA1 (72%), TP53 (71%), ATM (64%), BRCA2 (62%), RB1 (60%), Cyclin D1 (43%), and BRCAX (24%) and that in the older group being TP53 (66%), RB1 (63%), BRCA1 (56%), ATM (53%), BRCA2 (45%), Cyclin D1 (24%), and BRCAX (23%). Similar, differential correlations were also seen with several clinicopathological parameters, prognosis, and combinations of alterations among these genes in the two age groups. Differential frequencies and interrelationships of genetic alterations and prognoses in these two age groups indicate that the molecular pathways for the development of tumors in both age groups may not be similar, though the ultimate effect is deregulation of cell cycle checkpoints and defects in the DNA repair pathway.Annals of Surgical Oncology 01/2005; 11(12):1045-55. · 4.17 Impact Factor -
Article: Analysis of different deleted regions in chromosome 11 and their interrelations in early- and late-onset breast tumors: association with cyclin D1 amplification and survival.
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ABSTRACT: Previous studies have shown that younger women exhibit more aggressive pathologic features of breast cancer (BC) in comparison to older women; young age could be an independent predictor of adverse prognosis. In order to find any existing differences in the molecular progression of BC in both younger and older women, chromosome 11 (chr.11) was taken as a tool, due to its frequent deletion and amplification, particularly of CyclinD1 (CCND1) locus in BC. In the present work, the comparative analysis in the frequency of deletion in different regions in chr.11 and CCND1 amplification in BC in the two age groups was studied, as well as the interrelation and prognostic significance of these chromosomal alterations. The chr. 11 alterations were also studied in types of breast lesions other than carcinoma to see the prevalence of the alterations in these diseases. For this purpose, comparative deletion mapping of chr.11 using 17 microsatellite markers and CCND1 amplification was examined in 30 early-onset (</=40 years) and 33 late-onset (>40 years) breast carcinomas, as well as 11 other types of breast lesions. The frequency of deletion and CCND1 amplification was much higher in carcinomas than with other types of breast lesions. A total of six highly deleted regions, namely, 11p15.5, 11p11.2, 11q13.2, 11q22.3-23.1, 11q23.3-24.1, and 11q25, were identified in carcinomas of the two age groups. The 11q13.2 deletion and CCND1 amplification was comparatively higher in the carcinoma of younger women. The following significant associations were observed for (a) LOH at 11q25 with LOH at 11q13.2, 11q22.3-23.1, 11q23.3-24.1 and CCND1 amplification, respectively, and (b) LOH at 11p15.5 with LOH at 11q22.3-23.1 in carcinoma of younger women. On the other hand, the significant associations in older women were (a) LOH at 11q25 with LOH at 11q22.3-23.1, 11q23.3-24.1, respectively, and (b) LOH at 11q22.3-23.1 with LOH at 11q23.3-24.1. Deletion at 11q13.2 was also associated with reduced overall survival in the younger group, indicating its prognostic significance. It is evident from our data that the pattern of chromosomal alterations are not exactly same in the carcinomas in the two age groups. Differential interrelationship of the chromosomal alterations and prognosis in these two age groups indicate that the molecular pathogenesis of the carcinomas is not similar.Diagnostic Molecular Pathology 10/2004; 13(3):172-82. · 2.26 Impact Factor -
Article: Molecular study of clonality in multifocal and bilateral breast tumors.
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ABSTRACT: The clonal origin of multiple tumors in the same individual has long been debated. The main aim of this study is to find out whether multiple tumors in same individuals originated from a single clone. In our previous work (Pathol. Res. Pract. 199 (2003) 313-321), the deletion at chromosome1p36 was found to occur early because of common allelic loss in the bilateral tumors. In order to further investigate the findings about the clonality of tumors, eight tumors from four patients (two synchronous bilateral breast carcinoma [biBC], one case with breast carcinoma in one breast and multiple calcified fibroadenoma nodules in another breast, and one case with multifocal fibroadenosis in one breast) were subjected to polymerase chain reaction (PCR) to detect (a) loss of heterozygosity (LOH) and microsatellite size alterations (MA) using microsatellite markers distributed over five chromosomal arms 11p/q, 13q and 17p/q, and (b) Cyclin D1 amplification. Some markers were intragenic for BRCA1, BRCA2, BRCAX, ATM, TP53, and RB1. Although a few cases were studied, our findings suggest that in at least a proportion of patients multiple tumors may arise from a single clone.Pathology - Research and Practice 02/2004; 200(10):735-41. · 1.21 Impact Factor -
Article: Differential alterations of the genes in the CDKN2A-CCND1-CDK4-RB1 pathway are associated with the development of head and neck squamous cell carcinoma in Indian patients.
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ABSTRACT: The aim of this study was to analyse the alterations of the genes in the CDKN2A/CCND1/CDK4/RB1 pathway in the G1-S phase of the cell cycle during development of head and neck squamous cell carcinoma (HNSCC). The alterations of these genes were analysed in 22 dysplastic lesions, 26 stage-I/II and 33 stage-III/IV HNSCC tumours of Indian patients. The alterations [mutation, hypermethylation, homozygous deletion and loss of heterozygosity/microsatellite size alteration (LOH/MA)] in the CDKN2A were found to be highest in 57% of the samples, followed by CCND1 amplification and LOH/MA at the RB1 locus in 14% and 8.5% of the samples, respectively. No dominant CDK4 Arg24Cys mutation was seen in our samples. Comparatively high frequency of CDKN2A alterations (except homozygous deletion) was found in dysplastic head and neck lesions and remained almost constant or increased during progression of the tumour, whereas the homozygous deletion of CDKN2A and the alterations in CCND1 and RB1 genes were seen mainly in the later stages of the tumour. Our study suggested that mutation/hypermethylation/allelic alterations (LOH/MA) of CDKN2A were associated with the development of dysplastic head and neck lesions. All the other alterations might provide some cumulative effect during progression of later stages of the tumour to have selective growth advantages.Journal of Cancer Research and Clinical Oncology 12/2003; 129(11):642-50. · 2.56 Impact Factor -
Article: Deletion mapping of chromosome 1 in early onset and late onset breast tumors--a comparative study in eastern India.
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ABSTRACT: Younger women exhibit more aggressive pathologic features of breast cancer (BC) compared to their older counterparts. Young age has been shown to be an independent predictor of adverse prognosis. These findings have raised the question of whether these differences are also present at the genetic level. Twenty-five early onset (age < or = 40 years) tumors including 4 bilateral tumors, and 26 late onset (>40 years) breast tumors, including 2 bilateral tumors, were examined for loss of heterozygosity (LOH) at chromosome 1 using 11 polymorphic microsatellite markers. A comparative study revealed high frequencies of LOH in chr. 1p36 (61%), 1p31.3 (40%), 1p21.3 (50%) and 1q22-23.2 (56%) in a younger group, and chr. 1p36 (46%), 1p34.2 (48%), and 1q22-23.2 (52%) in an older group. These differences in LOH frequency in these two age groups were significant for chr. 1p21.3 (p = 0.025) only. These data suggest that the deletion pattern in early onset breast tumors is not fully identical to late onset breast tumors. Similar differential deletion patterns of LOH in the 5 highly deleted regions were seen in premenopausal and postmenopausal groups. An association was seen between LOH at chr. 1p34.2 and chr. 1q22-23.2 and higher grade of the tumors in older women. Among the highly deleted regions, the deletion at chr. 1p36 was found to occur early in both groups because of common allelic loss in the bilateral tumors.Pathology - Research and Practice 01/2003; 199(5):313-21. · 1.21 Impact Factor
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Institutions
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2003–2008
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Chittaranjan National Cancer Institute
Calcutta, Bengal, India
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