Wednesday, July 22, 2015

New ovarian cancer study on large structural variants based on TCGA data is out

We have recently published a study on ovarian cancer using whole genome sequence (control + tumor), RNA-Seq and microarray gene expression chip data from the same patients. Data was acquired from TCGA. The paper titles:

 "Integrated sequence and expression analysis of ovarian cancer structural variants underscores the importance of gene fusion regulation" (BMC medical genomicsPubmed)

Here is the brief summary:
  • First we designed an integrated bioinformatics workflow (Figure S1) to process and analyze the large volumes of genomic and transcriptomic data, and to detect structural variants (SVs) breakpoint accurately at the single nucleotide resolution. 
  • Using whole genome sequencing (WGS) data we first detected various classes of SVs and further classify them as 'germline derived' and 'somatically derived'.
  • Then based on their structure and underlyong genomic regions, determined their potential to create functional gene-fusions at the RNA level. 
  • Using RNA-Seq and micraoarray data, we measured the proportion potential gene-fusion forming SVs that actually get transcribed. 
  • The observations suggests existence of regulatory mechanism(s) that suppress the expression of more established germline SVs (could be segregating in natural population) but facilitates the selected somatically derived SVs at the RNA level in ovarian tumors.
  • Our findings resonate with the observations of Bueno et al. (Pubmed) that the expression of BCR-ABL gene fusion, a very well known tumor driver in non-solid tumors, can be regulated by the genetic and epigenetic silencing of miR-203
  • Our findings are also relevant to the fact that recent studies have found several gene-fusions that are considered as cancer biomarkers in healthy individuals. Simply put, not the ocurrance of SVs at the genomic level but the regulation of the expression of SVs at RNA level contributes to their biological and clinical significance in the onset and progression of cancer.
Feel free to contact me if have any questions and need some more details about from the paper.

1 comment:

  1. Interesting research http://www.biomedcentral.com/1755-8794/8/42/about

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