Comparative RNA sequencing analysis reveals KRAS A146P presence in rare form of Gliosarcoma
Physical and Biological Sciences
BIOL 195
Gliosarcoma is a rare and fast progressing brain cancer with a median survival rate of 9 months. This cancer's aggressive nature is due to its ability to metastasize rapidly either intracranially or to other parts of the central nervous system, through cerebrospinal fluid. Currently, the underlying genetic cause of this cancer is unknown, and there are few cases reporting patients with extracranial metastasis.
Uniquely, this study presents Patient X, who was diagnosed at University of Arkansas for Medical Sciences hospital with a form of gliosarcoma that originated in the brain and metastasized both intracranially and extracranially to the lungs. Patient X underwent several rounds of chemotherapy, radiation, and resections to eliminate the tumor. Additionally, drug treatments were administered based on targetable mutations found through tumor DNA sequencing, however these therapies were not successful. Given gliosarcoma's rarity and malignant features, DNA mutations present in the patient's tumor may not be the only cancer drivers.
RNA-sequencing technology is a powerful tool to identify gene expression abnormalities, expressed mutations, and gene fusions. However, generating high quality RNA sequencing data from biopsies can be challenging due to sample preservation methods used in the clinic, and requires optimization. We hypothesized that RNA sequencing can identify additional molecular targets for this tumor. This data shows, as one of the first research groups to perform RNA sequencing on extracranial gliosarcoma metastases, that comparison of the patient's metastasis to the primary tumor will further characterize this rare cancer.
I extracted RNA from four brain and two lung gliosarcoma Formalin-Fixed Paraffin-Embedded Tissue (FFPE) samples and performed Illumina RNA-sequencing. The sequencing data was compared to our cancer RNA sequencing Ribodeplete compendium using Treehouse Comparative Analysis of RNA expression (CARE) to identify relevant gene outliers. KRAS A146P was identified by CARE as a somatic mutation present in early brain samples and later lung metastasis, and was cross confirmed by DNA sequencing performed in the clinic. Additionally, CARE and clinicians findings both identified ERBB3 as an overexpressed transcript present 4 of the 6 samples, however samples were not correlated enough to the Treehouse tumor compendium to confirm accuracy of outlier analysis.
Our findings demonstrate that RNA sequencing can be used to identify molecular targets in rare cancers such as gliosarcoma.
