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Published on: April 11, 2016
Mutation Analysis of Nine Chordoma Specimens by Targeted Next-Generation Cancer Panel Sequencing
Carina Fischer1, Susanne Scheipl2, Agnes Zopf1
11. Red Cross Transfusion Service for Upper Austria, Krankenhausstraße 7, 4020 Linz, Austria.
Background:
Chordoma is a rare primary malignant bone tumour. Treatment options are mainly restricted to surgical excision, since chordomas are largely resistant to conventional ionising radiation and chemotherapy. Thus, there is a strong need to gain more thorough insights into the molecular biology and genetics of chordoma to allow for the development of new therapeutic options. We performed an ultra-deep sequencing analysis to find novel mutations in cancer associated genes in chordomas to date unseen with Sanger sequencing.
Material And Methods:
Nine chordomas (skull base (n=3), mobile spine (n=4), and sacrum/coccyx (n=2) were screened for mutations in 48 cancer genes using the Hot Spot Cancer Panel (Illumina). All putative mutations were compared against multiple databases (e.g. NCBI, COSMIC, PolyPhen, EGB, SIFT) and published Copy Number Variation (CNV) data for chordoma.
Results:
Our results showed mutations with a frequency above 5% in tumorsuppressor- and onco-genes, revealing new possible driver genes for chordomas. We detected three different variants accounting for 11 point mutations in three cancer associated genes (KIT, KDR and TP53). None of the detected mutations was found in all samples investigated. However, all genes affected interact or are connected in pathway analysis. There were no correlations to already reported CNVs in the samples analysed.
Conclusions:
We identified mutations in the associated genes KIT, KDR, and TP53. These mutations have been described previously and have been predicted to be tolerated. Further results on a larger series are warranted. The driver mechanisms of chordoma still have to be identified.
Insights
This study identified mutations in KIT, KDR, and TP53 genes in chordoma, a rare bone cancer. Further research is needed to understand the driver mechanisms and develop new therapies.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Chordoma is a rare bone tumor resistant to conventional treatments.
- Novel therapeutic strategies require deeper understanding of chordoma's molecular and genetic basis.
- Ultra-deep sequencing can identify previously undetected mutations.
Purpose of the Study:
- To identify novel mutations in cancer-associated genes in chordoma using ultra-deep sequencing.
- To uncover potential new driver genes for chordoma development.
- To explore new therapeutic targets for chordoma.
Main Methods:
- Nine chordoma samples (skull base, mobile spine, sacrum/coccyx) were analyzed.
- Mutation screening was performed on 48 cancer genes using the Hot Spot Cancer Panel.
- Detected mutations were cross-referenced with multiple genetic databases and copy number variation data.
Main Results:
- Mutations with >5% frequency were found in tumor suppressor and oncogenes.
- Eleven point mutations were identified in three cancer-associated genes: KIT, KDR, and TP53.
- Pathway analysis indicated interactions among the affected genes; no correlation with reported copy number variations was found.
Conclusions:
- Mutations in KIT, KDR, and TP53 were identified in chordoma.
- These previously described mutations are predicted to be tolerated.
- Further studies on larger cohorts are necessary to elucidate chordoma's driver mechanisms.
