Breast cancer is the most common malignancy among women, with the highest incidence rate worldwide. Dysregulation of long noncoding RNAs during the preliminary stages of breast carcinogenesis is poorly understood. In this study, we performed RNA sequencing to identify long noncoding RNA expression profiles associated with early‐stage breast cancer. RNA sequencing was performed on six invasive ductal carcinoma (IDC) tissues along with paired normal tissue samples, seven ductal carcinoma in situ tissues, and five apparently normal breast tissues. We identified 375 differentially expressed lncRNAs (DElncRNAs) in IDC tissues compared to paired normal tissues. Antisense transcripts (~ 58%) were the largest subtype among DElncRNAs. About 20% of the 375 DElncRNAs were supported by typical split readings leveraging their detection confidence. Validation was performed in n = 52 IDC and paired normal tissue by qRT‐PCR for the identified targets (ADAMTS9‐AS2, EPB41L4A‐AS1, WDFY3‐AS2, RP11‐295M3.4, RP11‐161M6.2, RP11‐490M8.1, CTB‐92J24.3, and FAM83H‐AS1). We evaluated the prognostic significance of DElncRNAs based on TCGA datasets and report that overexpression of FAM83H‐AS1 was associated with patient poor survival. We confirmed that the downregulation of ADAMTS9‐AS2 in breast cancer was due to promoter hypermethylation through in vitro silencing experiments and pyrosequencing.

Breast cancer is a major cause of cancer‐related death in women worldwide. Non‐coding RNAs are a potential resource to be used as an early diagnostic biomarker for breast cancer. Circular RNAs are a recently identified group of non‐coding RNA with a significant role in disease development with potential utility in diagnosis/prognosis in cancer. In this study, we identified 26 differentially expressed circular RNAs associated with early‐stage breast cancer. RNA sequencing and two circRNA detection tools (find_circ and DCC) were used to understand the circRNA expression signature in breast cancer. We identified hsa_circ_0006743 (circJMJD1C) and hsa_circ_0002496 (circAPPBP1) to be significantly up‐regulated in early‐stage breast cancer tissues. Co‐expression analysis identified four pairs of circRNA‐miRNA (hsa_circ_0023990 : hsa‐miR‐548b‐3p, hsa_circ_0016601 : hsa_miR‐1246, hsa_circ_0001946 : hsa‐miR‐1299 and hsa_circ_0000117:hsa‐miR‐502‐5p) having potential interaction. The miRNA target prediction and network analysis revealed mRNA possibly regulated by circRNAs. We have thus identified circRNAs of diagnostic implications in breast cancer and also observed circRNA‐miRNA interaction which could be involved in breast cancer development.

The methylation of cytosine residues that precede adenine/thymine or other cytosine nucleotides instead of guanine in DNA is known as non-CpG methylation. It is a pronounced epigenetic modification with a central role in gene regulation similar to CpG methylation. Due to technological limitations, the locus-specific role of non-CpG methylation was scarcely understood. At present, high-throughput analyses and improved enrichment methods can elucidate the role of genome-wide non-CpG methylation distributions. Although the functional basis of non-CpG methylation in regulating gene expression control is known, its role in cancer development is yet to be ascertained. This review sheds light on the possible mechanism of non-CpG methylation in embryos and developed tissues with a special focus on cancer development and progression. In particular, the maintenance and alteration of non-CpG methylation levels and the crucial factors that determine this level of non-CpG methylation and its functional role in cancer are discussed.

Targeted Resequencing of 30 Genes Improves the Detection of Deleterious Mutations in South Indian Women with Breast and/or Ovarian Cancers Targeted resequencing;BRCA1/BRCA2/RAD50/RAD52;ATM;TP53BP1;deleterious mutations; Background: We earlier used PCR-dHPLC for mutation analysis of BRCA1 and BRCA2. In this article we report application of targeted resequencing of 30 genes involved in hereditary cancers. Materials and Methods: A total of 91 patient samples were analysed using a panel of 30 genes in the Illumina HiScan SQ system. CLCBio was used for mapping reads to the reference sequences as well as for quality-based variant detection. All the deleterious mutations were then reconfirmed using Sanger sequencing. Kaplan Meier analysis was conducted to assess the effect of deleterious mutations on disease free and overall survival. Results: Seventy four of the 91 samples had been run earlier using the PCR-dHPLC and no deleterious mutations had been detected while 17 samples were tested for the first time. A total of 24 deleterious mutations were detected, 11 in BRCA1, 4 in BRCA2, 5 in p53, one each in RAD50, RAD52, ATM and TP53BP1. Some 19 deleterious mutations were seen in patients who had been tested earlier with PCR-dHPLC [19/74] and 5/17 in the samples tested for the first time, Together with our earlier detected 21 deleterious mutations in BRCA1 and BRCA2, we now had 45 mutations in 44 patients. BRCA1c.68_69delAG;p.Glu23ValfsX16 mutation was the most common, seen in 10/44 patients. Kaplan Meier survival analysis did not show any difference in disease free and overall survival in the patients with and without deleterious mutations. Conclusions: The NGS platform is more sensitive and cost effective in detecting mutations in genes involved in hereditary breast and/or ovarian cancers.

Cancers of the upper aerodigestive tract (UADT) are common forms of malignancy associated with tobacco and alcohol exposures, although human papillomavirus and nutritional deficiency are also important risk factors. While somatically acquired DNA methylation changes have been associated with UADT cancers, what triggers these events and precise epigenetic targets are poorly understood. In this study, we applied quantitative profiling of DNA methylation states in a panel of cancer-associated genes to a case-control study of UADT cancers. Our analyses revealed a high frequency of aberrant hypermethylation of several genes, including MYOD1, CHRNA3 and MTHFR in UADT tumors, whereas CDKN2A was moderately hypermethylated. Among differentially methylated genes, we identified a new gene (the nicotinic acetycholine receptor gene) as target of aberrant hypermethylation in UADT cancers, suggesting that epigenetic deregulation of nicotinic acetycholine receptors in non-neuronal tissues may promote the development of UADT cancers. Importantly, we found that sex and age is strongly associated with the methylation states, whereas tobacco smoking and alcohol intake may also influence the methylation levels in specific genes. This study identifies aberrant DNA methylation patterns in UADT cancers and suggests a potential mechanism by which environmental factors may deregulate key cellular genes involved in tumor suppression and contribute to UADT cancers.