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A pilot study on the prevalence of DNA palindromes in breast cancer genomes.

Research paper by Sandeep S Subramanian, Srilakshmi S Chaparala, Viji V Avali, Madhavi K MK Ganapathiraju

Indexed on: 25 Jan '17Published on: 25 Jan '17Published in: BMC Medical Genomics



Abstract

DNA palindromes are a unique pattern of repeat sequences that are present in the human genome. It consists of a sequence of nucleotides in which the second half is the complement of the first half but appearing in reverse order. These palindromic sequences may have a significant role in DNA replication, transcription and gene regulation processes. They occur frequently in human cancers by clustering at specific locations of the genome that undergo gene amplification and tumorigenesis. Moreover, some studies showed that palindromes are clustered in amplified regions of breast cancer genomes especially in chromosomes (chr) 8 and 11. With the large number of personal genomes and cancer genomes becoming available, it is now possible to study their association to diseases using computational methods. Here, we conducted a pilot study on chromosomes 8 and 11 of cancer genomes to identify computationally the differentially occurring palindromes.We processed 69 breast cancer genomes from The Cancer Genome Atlas including serum-normal and tumor genomes, and 1000 Genomes to serve as control group. The Biological Language Modelling Toolkit (BLMT) computes palindromes in whole genomes. We developed a computational pipeline integrating BLMT to compute and compare prevalence of palindromes in personal genomes.We carried out a pilot study on chr 8 and chr 11 taking into account single nucleotide polymorphisms, insertions and deletions. Of all the palindromes that showed any variation in cancer genomes, 38% of what were near breast cancer genes happened to be the most differentiated palindromes in tumor (i.e. they ranked among the top 25% by our heuristic measure).These results will shed light on the prevalence of palindromes in oncogenes and the mutations that are present in the palindromic regions that could contribute to genomic rearrangements, and breast cancer progression.