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Recent advances in next generation sequencing (NGS) technologies have heralded the genomic research. From the good-old inferring differentially expressed genes (DEG) using microarray to the current adage NGS-based whole transcriptome or RNA-Seq pipelines, there have been advances and improvements. With several bioinformatics pipelines for analysing RNA-Seq on rise, inferring the candidate DEGs prove to be a cumbersome approach as one may have to reach consensus among all the pipelines. To Check this, we have benchmarked the well known cufflinks-cuffdiff pipeline on a set of datasets and outline it in the form of a protocol where researchers interested in performing whole transcriptome shotgun sequencing and it’s downstream analysis can better disseminate the analysis using their datasets.

In the recent past, there has been a rise in Prostate Cancer (PCa) in Asia, particularly India. Although systematic reviews on PCa have dealt on the genetics, genomics and the environmental influence in causal of PCa, no predictive analytics in comparing the PCa from Caucasian, American to Asian population was attempted. In this review article, we have attempted to elaborate this aspect of PCa and deliberated on challenges related to next generation sequencing methods of PCa’s manifestation when compared to the west.

Bladder cancer is the fourth most frequently diagnosed malignant neoplasm and cause of cancer-related deaths in men and eighth in women. Patients with bladder cancer undergo repeated cystoscopic examinations of the bladder to monitor for tumour recurrence which is invasive, costly and lacks accuracy. Therefore, the development of non-invasive urine based tests for the early detection of bladder cancer would be of tremendous benefit to both patients and healthcare systems. A number of urine based markers are available for the early diagnosis of bladder cancer. The diagnosis of bladder cancer relies on identifying malignant cells in the urine. All urinary markers have a higher sensitivity as compared with cytology but they score lower in specificity. Many soluble and cell based markers have been developed. Only two of the soluble and cell based markers have obtained the Food and Drug Administration approval. In the current review, the most recent literature of urinary markers is summarised. This article reports some of the more prominent urine markers and new technologies used nowadays.

Bladder cancer is the fourth most frequently diagnosed malignant neoplasm and cause of cancer-related deaths in men and eighth in women. Patients with bladder cancer undergo repeated cystoscopic examinations of the bladder to monitor for tumour recurrence which is invasive, costly and lacks accuracy. Therefore, the development of non-invasive urine based tests for the early detection of bladder cancer would be of tremendous benefit to both patients and healthcare systems. A number of urine based markers are available for the early diagnosis of bladder cancer. The diagnosis of bladder cancer relies on identifying malignant cells in the urine. All urinary markers have a higher sensitivity as compared with cytology but they score lower in specificity. Many soluble and cell based markers have been developed. Only two of the soluble and cell based markers have obtained the Food and Drug Administration approval. In the current review, the most recent literature of urinary markers is summarised. This article reports some of the more prominent urine markers and new technologies used nowadays.

Occult hepatitis C viral infection (OHCI) is a newly reported pathological entity associated with increased risk of developing hepatocellular carcinoma and lymphoproliferative disorders. Although hepatocytes are the primary sites of viral replication, hepatitis C virus is potentially lymphotropic, invading and propagating in cells of the immune system. Lymphocytes, the extrahepatic viral reservoirs, are differentially implicated in the occult and the active forms of the disease. This study aimed to elucidate the implications of mitochondrial oxidative stress on the immune pathophysiological mechanisms of OHCI. We herein report that OHCI induces mitochondrial oxidative stress, leading to DNA double-strand breaks and elicitation of a phosphoinositol 3-kinase-mediated cellular response in peripheral blood lymphocytes. Compared to controls, OHCI subjects showed higher accumulation of pATM, pATR, γH2AX, and p-p53, along with active recruitment of repair proteins (Mre11, Rad50, and Nbs1) and altered mitochondrial DNA content. Increased mitochondrial membrane depolarization and circulating nucleosome levels along with chromatid-type aberrations and decreased T-cell proliferative index observed in the OHCI group further indicated that this damage might lead to Bax-triggered mitochondria-mediated cellular apoptosis. Together our results provide the mechanistic underpinnings of mitochondrial dysfunction in OHCI, a previously unknown paradigm, for explaining the immune pathogenesis in a redox-dependent manner.

The toxic response of cultured human colon epithelial-FHC cells to methyl isocyanate was investigated with regard to genomic instability. Qualitative and quantitative assessments of the extent of phosphorylation of DNA damage signaling factors such as ATM, gammaH2AX and p53, was increased in treated cells compared to controls. At the same time, many treated cells were arrested at the G2/M phase of the cell cycle, and had an elevated apoptotic index and increased inflammatory cytokine levels. Cytogenetic analyses revealed varied chromosomal anomalies, with abnormal expression of pericentrin protein. Analysis through ISSR PCR demonstrated increased microsatellite instability. The results imply that isocyanates can cause genomic instability in colonocytes.

Gallbladder carcinoma is an uncommon, but highly malignant tumor, with poor prognostic, and diagnostic manifestations in early stages. The Indian Council of Medical Research reported increased incidence of gallbladder carcinoma in the surviving population of the Bhopal gas tragedy that involved exposure of more than 500,000 people to methyl isocyanate gas. The severity of exposure, and increased multi-systemic morbidity in the survivors stimulated us to examine the molecular changes leading to gallbladder carcinoma. Surgically resected samples (N = 40) of gallbladder carcinoma were studied for the p53, Rad50, and cyclin-E expression by immunohistofluorescence bioimaging. Among the 40 samples, 23, 11, and 10 showed p53, Rad50, and cyclin-E expression, respectively, in moderately differentiated adenocarcinomas, demonstrating the prevalence and invasiveness of this disease in the methyl isocyanate-exposed population (P = 0.0009). Nevertheless, co-expression of Rad50, and cyclin-E with p53 was absent in adenomas with dysplasia, demonstrating their independent roles. We conclude that there was altered expression of p53, Rad50, and cyclin-E in the malignant transformation of gallbladder carcinoma in this methyl isocyanate gas-exposed cohort. Hence, these proteins may be useful as markers to identify premalignant lesions that are likely to progress into malignant adenocarcinoma.

DNA methyltransferase 1 (DNMT1) is a relatively large protein family responsible for maintenance of normal methylation, cell growth and survival in mammals. Toxic industrial chemical exposure associated methylation misregulation has been shown to have epigenetic influence. Such misregulation could effectively contribute to cancer development and progression. Methyl isocyanate (MIC) is a noxious industrial chemical used extensively in the production of carbamate pesticides. We here applied an in silico molecular docking approach to study the interaction of MIC with diverse domains of DNMT1, to predict cancer risk in the Bhopal population exposed to MIC during 1984. For the first time, we investigated the interaction of MIC and its hydrolytic product (1,3-dimethylurea) with DNMT1 interacting (such as DMAP1, RFTS, and CXXC) and catalytic (SAM, SAH, and Sinefungin) domains using computer simulations. The results of the present study showed a potential interaction of MIC and 1,3-dimethylurea with these domains. Obviously, strong binding of MIC with DNMT1 interrupting normal methylation will lead to epigenetic alterations in the exposed humans. We suggest therefore that the MIC- exposed individuals surviving after 1984 disaster have excess risk of cancer, which can be attributed to alterations in their epigenome. Our findings will help in better understanding the underlying epigenetic mechanisms in humans exposed to MIC.

The molecular alterations are considered to play an important role in the both carcinogenesis and biological behavior of a variety of human malignancies. However, cancer of gallbladder is an obscured phenomenon and highly malignant with a poor survival due to underprivileged diagnosis. Tissues of 92 cases of gallbladder cancer patients (31 men and 61 women, age range 16-85 yrs, mean age 45.83 ± 1.50 yrs) were examined for microsatellite instability (MSI) of six microsatellite markers (D16S539, D13S317, D7S820, F13A01, FES/FPS, vWA) and apoptosis of malignant epithelial cells through M30CytoDEATH assay. Analysis of microsatellite markers revealed 08.7% (08/92) in gallbladder cancer, in which 10.0% (07/70) instability found in adenocarcinoma. The sensitivity of this test in adenocarcinoma, adenosquamous carcinaoma and adenoma with dysplasia was found to be 10.0%, 00.0% and 08.3% respectively suggesting its role in the multistage disease invasiveness. The immunohistochemical examination confirmed the presence of CK18 in moderately, well and poorly differentiated adenocarcinoma with the frequency of viz., 18.8%, 15.4% and 11.1% respectively showing positive sign of apoptosis. The mixed chimerism of STR loci and positive staining of caspase cleaved CK18 in epithelial cells of the gallbladder cancer tissues showed their independent and noteworthy character in the gallbladder carcinogenesis. Further investigations are in progress to undertake similar studies on archived tumor tissues of varied origins and forms. These might also provide modalities to translate forceful and reproducible strategies for defined clinical utility.

Bladder cancer is a major health-care concern. A successful treatment of bladder cancer depends on its early diagnosis at the initial stage. Genetic instability is an essential early step toward the development of bladder cancer. This instability is found more often at the chromosomal level than at the nucleotide level. Microsatellite and chromosomal instability markers can be used as a prognostic marker for screening bladder cancer. Bladder cancer can be distinguished in two different categories according to genetic instability: Cancers with chromosomal level instability and cancers with nucleotide level instability. Deoxyribonucleic acid (DNA) mismatch repair (MMR) system and its correlation with other biologic pathway, both are essential to understand the basic mechanisms of cancer development. Microsatellite instability occurs due to defects in DNA MMR genes, including human mutL homolog 1 and human mutL homolog 2. Chromosomal alterations including deletions on chromosome 3, 8, 9, 11, 13, 17 have been detected in bladder cancer. In the current review, the most recent literature of genetic instability in urinary bladder cancer has been summarized.