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E-Poster Display

387P - Detection of 1p/19q deletion in gliomas with high accuracy by combining sequencing depth and heterozygous SNV allele frequency

Date

17 Sep 2020

Session

E-Poster Display

Topics

Tumour Site

Central Nervous System Malignancies

Presenters

Peng Zhao

Citation

Annals of Oncology (2020) 31 (suppl_4): S396-S408. 10.1016/annonc/annonc269

Authors

P. Zhao1, Z. Wu2, Q. Duan3, L. Yan3, W. Deng2, N. Luo3

Author affiliations

  • 1 Department Of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 250021 - Jinan/CN
  • 2 Department Of Bioinformatics, Jiangsu Simcere Diagnostics Co., Ltd, 210042 - Nanjing/CN
  • 3 Department Of Medicine, Jiangsu Simcere Diagnostics Co., Ltd, 210042 - Nanjing/CN

Resources

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Abstract 387P

Background

1p/19q co-deletion is an important diagnosis and prognosis biomarker of glioma. Fluorescence in situ hybridization (FISH), as the golden standard method, is often unachievable for sample preparation difficulties. In addition, the accuracy is limited because only a few specific genomic loci are detected to represent the status of whole chromosomal arms. Here we propose a sequencing-based method that combines coverage depth and allele frequency of heterozygous SNVs, to improve the detection of 1p/19q co-deletion.

Methods

We designed a DNA capture kit, which covers the whole 1p and 19q chromosomal arms with well-distributed probes, about one per 500kb region. Fifty-four negative and 20 positive samples of 1p/19q co-deletion, all confirmed by FISH, were involved to establish the method. DNA libraries of the samples were captured by the kit, and then sequenced on Illumina platform. After mapping the sequenced reads to the human reference genome, cumulative Stouffer's Z-scores of sequencing depth at all probe loci were calculated and compared between positive samples and negative control samples, and allele frequencies of all heterozygous SNVs on the two chromosomal arms were calculated. The 1p/19q deletion was defined as that the Z-score exceeds the cutoff and the allele frequency distribution deviates from theoretical heterozygous allele frequency 50%.

Results

Without combining information of heterozygous SNV, our method generated comparable results as other popular tools, such as CNVkit. We got 100% sensitivity and 98.1% specificity on 1p-arm and 100% sensitivity and 96.2% specificity on 19q-arm. By manually checking the false-positive cases, we confirmed that their allele frequency distribution of heterozygous SNVs deviated from 50%, indicating that the false LOH result should be caused by the fluctuation of sequencing. By combining heterozygous SNV allele frequency, the specificity of 1p and 19q detection was increased to 100% and 98%.

Conclusions

We developed a new method for detection of 1p/19q deletion with high accuracy, by improving both the capture kit design and bioinformatics algorithm to incorporate both sequencing depth and allele frequency of heterozygous SNVs.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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