Many mutations in breast cancer exome sequences alter susceptibility to infections. An exhaustive analysis of all the mutations in exomes from 103 breast cancer cases found that more than 1,000 genes have a published association with some kind of infection, including all known tumor viruses. Altered susceptibility to infection was identified as a common thread connecting breast cancer mutations in genes traditionally classified as coding for diverse functions, including cell immunity, cell architectural barriers, stromal interactions, cell adhesion, DNA damage responses, translation, cell cycle control, metabolism, homeostasis, transport, and neurosensing. Infections and mutations can both contribute to cancer because they deregulate the same pathways. In many cases, infections make a contribution to cancer that is either known or biologically plausible. Interventions may be possible to prevent occult infections from cooperating with mutations to cause further cancer, metastasis, or other complications. The emerging list of infection–gene mutation associations is readily scalable to routine testing of large human data sets.
Nucleotide binding site leucine rich repeat (NBS-LRR) gene encoding proteins are the major biotic stress resistance genes of rice and Arabidopsis thaliana. Upstream sequences of 206 entire NBS-LRR genes of Arabidopsis and 120 genes of rice were analyzed with three highly reliable motif prediction tools for enhanced accuracy of prediction and characterization of potential transcription factor binding motifs (TFBMs). A total of 36 and 30 novel, strong TFBMs were discovered from NBS-LRR genes of rice and A. thaliana, respectively. All the motifs identified in these sequences were analyzed for their positional conservation and the possible motif network associations were also identified. Further, the probability of the presence of motifs in these NBS-LRR genes were validated and statistically tested. Although Arabidopsis NBS-LRR sequences showed 76.3% similarity with rice sequences at motif level, the analysis revealed that rice sequences have many unique TFBMs and are more evolved in gene expression mechanisms. The study also provided a list of novel candidate motifs for these genes, which will be a good resource for experimental validation. A novel strategy of prediction of gene expression based on motif arrangement was also demonstrated in this study. The findings of this study, such as the motifs’ positional conservation, architecture, etc. offered new biological insights into the role of TFBMs in the regulation of resistance genes.
Infections may play a larger role in breast cancer than previously believed, especially if normal breast cell architecture and immune defenses have been weakened by gene mutations. Mutated genes in 289 breast cancers were compared with mutated genes in model viral and non-viral cancers. DNA sequences were obtained from publicly available data. Mutated genes in breast cancers were just as likely to be found in viral cancers as in non-viral cancers. Breast, viral, and non-viral cancers all had damage to genes encoding essential immune functions and physical barriers to cell infection. Potentially, damage to these protective genes can suppress control of cancer-associated viruses and open easier routes for infectious particles. Genes that provide protection against cancer viruses and form barriers against infection were damaged in every breast, viral, and non-viral cancer tested. Breast and other cancer cells may already harbor infections. Gaps in immunity or in infection barriers caused by distinct individual sets of mutations make cancer cells more susceptible than normal cells to infections that can exploit the cancer mutations. Other infections may be less likely because mutations have altered host proteins the other infection requires. Understanding gaps in cell defenses may enable therapy that more specifically destroys cancer cells and preserves normal cells.
Autoimmune enteropathy (AIE) is a rare clinical condition characterized by intractable diarrhea of early childhood.¹ While AIE can feature both simple Mendelian inheritance or a complex multifactorial pattern, the pathogenesis remains unclear in many cases.² This is important for providing an accurate recurrence risk as affected individuals survive until adulthood and have children. Here, we describe a father and son with AIE who had clinically distinct courses. Exome sequencing has revealed a novel missense variant, c.2147C>T; (p.Thr716Met) in the signal transducer and activator of transcription 3 gene (STAT3) in both the father and son, consistent with autosomal dominant inheritance. STAT3 regulates immune reactions, and mutations in this gene have previously been associated with autoimmunity and Hyper IgE syndrome, but not AIE. Further studies are needed to assess the functional effect of this variant as it relates to the phenotype.
CITATION: friedenson. Correction to reference numbers in: “many Breast Cancer mutations Parallel mutations in Known Viral Cancers”. Journal of Genomes and Exomes 2014:3 37 doi:10.4137/JGe.s22513. TYPE: Corrigendum COPYRIGHT: © the authors, publisher and licensee libertas academica limited. This is an open-access article distributed under the terms of the Creative Commons CC-BY-nC 3.0 license. CORRESPONDENCE: molmeddoc@yahoo.com; bernief@uic.edu
