Objective
To understand the chemotherapy response program in ovarian cancer cells at deep transcript sequencing levels.
Methods
Two next-generation sequencing technologies—MPSS (massively parallel signature sequencing) and SBS (sequencing by synthesis) — were used to sequence the transcripts of IGROV1 and IGROV1-CP cells, and to sequence the transcripts of a highly chemotherapy responsive and a highly chemotherapy resistant ovarian cancer tissue.
Results
We identified 3,422 signatures (2957 genes) that are significantly different between IGROV1 and IGROV1-CP cells (P <0.001). Gene Ontology (GO) term GO:0001837 (epithelial to mesenchymal transition) and GO:0034330 (cell junction assembly and maintenance) are enriched in genes that are over expressed in IGROV1-CP cells while apoptosis related GO terms are enriched in genes over expressed in IGROV1 cells. We identified 1,187 tags (corresponding to 1,040 genes) that are differentially expressed between the chemotherapy responsive and the persistently chemotherapy resistant ovarian cancer tissues. GO term GO:0050673 (epithelial cell proliferation) and GO:0050678 (regulation of epithelial cell proliferation) are enriched in the genes over expressed in the chemotherapy resistant tissue while the GO:0007229 (integrin-mediated signaling pathway) is enriched in the genes over expressed in the chemotherapy sensitive tissue. An integrative analysis identified 111 common differentially expressed genes including two bone morphogenetic proteins (BMP4 and BMP7), six solute carrier proteins (SLC10A3, SLC16A3, SLC25A1, SLC35B3, SLC7A5 and SLC7A7), transcription factor POU5F1 (POU class 5 homeobox 1), and KLK10 (kallikrein-related peptidase 10). A network analysis revealed a subnetwork with three gene BMP7, NR2F2 and AP2B1 that were consistently over expressed in the chemoresistant tissue or cells compared to the chemosensitive tissue or cells.
Conclusion
Our database offers the first comprehensive view of the digital transcriptomes of ovarian cancer cell lines and tissues with different chemotherapy response phenotypes.
In β-thalassemia, point mutations in the β-globin gene are largely responsible for either decreased or no β-globin synthesis. The β-globin gene has three exons and two introns. The molecular characterization of β-thalassemia is absolutely necessary for carrier screening, for genetic counseling, and to offer prenatal diagnosis. The objective of the present study was to identify the rare mutations in β-globin gene of β-thalassemia patients. We have sequenced the entire β-globin gene in 36 clinically identified thalassemia patients from the Karnataka region using polymerase chain reaction and sequencing. Our analysis revealed 11 β-thalassemia variants. The most common being IVSII-16 G>C, IVSI-5G>C, IVSII-74 T>G, codon 3 (T>C), and Poly A site (T>C). In addition, we have also documented a novel deletion at codon 6 (-CT) (HBB:c.16delCT). These data are useful in future molecular screening of the population for implementing a thalassemia prevention and control program. Further it is found that family studies and comprehensive hematological analyses would provide useful insights for accurate molecular diagnosis of thalassemia phenotype and offers an interesting subject for further investigations in the Indian populations.
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