Biomedical subjects

Ritu Roydasgupta

Publications and source records attributed to Ritu Roydasgupta.

4 recordsLinked to original sources

PubMed2007

Chromosomal aberrations in angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma unspecified: A matrix-based CGH approach.

Angioimmunoblastic T-cell lymphoma (AILT) is a histopathologically well-defined entity. However, despite a number of cytogenetic studies, the genetic basis of this lymphoma entity is not clear. Moreover, there is an overlap to some cases of peripheral T-cell lymphoma unspecified (PTCL-u) in respect to morphological and genetic features. We used array-based comparative genomic hybridization (CGH) to study genetic imbalances in 39 AILT and 20 PTCL-u. Array-based CGH revealed complex genetic imbalances in both AILT and PTCL-u. Chromosomal imbalances were more frequent in PTCL-u than in AILT and gains exceeded the losses. The most recurrent changes in AILT were gains of 22q, 19, and 11p11-q14 (11q13) and losses of 13q. The most frequent changes in PTCL-u were gains of 17 (17q11-q25), 8 (involving the MYC locus at 8q24), and 22q and losses of 13q and 9 (9p21-q33). Interestingly, gains of 4q (4q28-q31 and 4q34-qtel), 8q24, and 17 were significantly more frequent in PTCL-u than in AILT. The regions 6q (6q16-q22) and 11p11 were predominantly lost in PTCL-u. Moreover, we could identify a recurrent gain of 11q13 in both AILT and PTCL-u, which has previously not been described in AILT. Trisomies 3 and 5, which have been described as typical aberrations in AILT, were identified only in a small number of cases. In conclusion, CGH revealed common genetic events in peripheral T-cell lymphomas as well as peculiar differences between AILT and PTCL-u.

Chromosome Aberrations↗

PubMed2006

Chromosomal instability in microsatellite-unstable and stable colon cancer.

PURPOSE: The genomic instability in colon cancer can be divided into at least two major types, microsatellite instability (MSI) or chromosomal instability (CIN). Although initially felt to be mutually exclusive, recent evidence suggests that there may be overlap between the two. The aim of this study was to identify chromosomal alterations at high resolution in sporadic colon cancers with high-level microsatellite instability (MSI-H) and to compare them to those present in a set of matched microsatellite stable (MSS) tumors. EXPERIMENTAL DESIGN: Array-based comparative genomic hybridization was used to analyze a set of 23 sporadic MSI-H and 23 MSS colon cancers matched for location, gender, stage, and age. The arrays consisted of 2,464 bacterial artificial chromosome clones. RESULTS: MSI and MSS colon cancers differed significantly with respect to frequency and type of chromosomal alterations. The median fraction of genome altered was lower among MSI-H tumors than MSS tumors (2.8% versus 30.7%, P=0.00006). However, the MSI-H tumors displayed a range of genomic alterations, from the absence of detectable alterations to extensive alterations. Frequent alterations in MSI-H tumors included gains of chromosomes 8, 12, and 13, and loss of 15q14. In contrast, the most frequent alterations in MSS tumors were gains of 7, 13, 8q, and 20, and losses of 8p, 17p, and 18. A small, previously uncharacterized, genomic deletion on 16p13.2, found in 35% of MSI-H and 21% of MSS tumors, was confirmed by fluorescence in situ hybridization. CONCLUSION: MSI and CIN are not mutually exclusive forms of genomic instability in sporadic colon cancer, with MSI tumors also showing varying degrees of CIN.

Adenocarcinoma↗

PubMed2006

Genomic and transcriptional aberrations linked to breast cancer pathophysiologies.

This study explores the roles of genome copy number abnormalities (CNAs) in breast cancer pathophysiology by identifying associations between recurrent CNAs, gene expression, and clinical outcome in a set of aggressively treated early-stage breast tumors. It shows that the recurrent CNAs differ between tumor subtypes defined by expression pattern and that stratification of patients according to outcome can be improved by measuring both expression and copy number, especially high-level amplification. Sixty-six genes deregulated by the high-level amplifications are potential therapeutic targets. Nine of these (FGFR1, IKBKB, ERBB2, PROCC, ADAM9, FNTA, ACACA, PNMT, and NR1D1) are considered druggable. Low-level CNAs appear to contribute to cancer progression by altering RNA and cellular metabolism.

Breast Neoplasms↗

PubMed2005

Bladder cancer stage and outcome by array-based comparative genomic hybridization.

PURPOSE: Bladder carcinogenesis is believed to follow alternative pathways of disease progression driven by an accumulation of genetic alterations. The purpose of this study was to evaluate associations between measures of genomic instability and bladder cancer clinical phenotype. EXPERIMENTAL DESIGN: Genome-wide copy number profiles were obtained for 98 bladder tumors of diverse stages (29 pT(a), 14 pT1, 55 pT(2-4)) and grades (21 low-grade and 8 high-grade superficial tumors) by array-based comparative genomic hybridization (CGH). Each array contained 2,464 bacterial artificial chromosome and P1 clones, providing an average resolution of 1.5 Mb across the genome. A total of 54 muscle-invasive cases had follow-up information available. Overall outcome analysis was done for patients with muscle-invasive tumors having "good" (alive >2 years) versus "bad" (dead in <2 years) prognosis. RESULTS: Array CGH analysis showed significant increases in copy number alterations and genomic instability with increasing stage and with outcome. The fraction of genome altered (FGA) was significantly different between tumors of different stages (pT(a) versus pT1, P = 0.0003; pT(a) versus pT(2-4), P = 0.02; and pT1 versus pT(2-4), P = 0.03). Individual clones that differed significantly between different tumor stages were identified after adjustment for multiple comparisons (false discovery rate < 0.05). For muscle-invasive tumors, the FGA was associated with patient outcome (bad versus good prognosis patients, P = 0.002) and was identified as the only independent predictor of overall outcome based on a multivariate Cox proportional hazards method. Unsupervised hierarchical clustering separated "good" and "bad" prognosis muscle-invasive tumors into clusters that showed significant association with FGA and survival (Kaplan-Meier, P = 0.019). Supervised tumor classification (prediction analysis for microarrays) had a 71% classification success rate based on 102 unique clones. CONCLUSIONS: Array-based CGH identified quantitative and qualitative differences in DNA copy number alterations at high resolution according to tumor stage and grade. Fraction genome altered was associated with worse outcome in muscle-invasive tumors, independent of other clinicopathologic parameters. Measures of genomic instability add independent power to outcome prediction of bladder tumors.

Chromosome Mapping↗