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3. Application of optical genome mapping to identify samples with homologous recombination deficiency.
- Source :
-
Cancer Genetics . 2023 Supplement 1, Vol. 278, pN.PAG-N.PAG. 1p. - Publication Year :
- 2023
-
Abstract
- Certain cancer treatments have been shown to be effective in killing cancer cells exhibiting genome instability signatures indicative of homologous recombination deficiency (HRD). There are three measurements of HRD signatures commonly employed: loss of heterozygosity (HRD-LOH), telomeric allelic imbalance (TAI) and large-scale state transition (LST). Current genomic technologies lack sensitivity to capture the full extent of somatic variants related to HRD and this limits their sensitivity. Here, optical genome mapping (OGM) was used to detect large structural variants (SVs) and calculate a HRD score. OGM captures high molecular weight DNA to call SVs by aligning these molecules to the public reference genome. Subsequently, an automated algorithm was developed to compute the HRD score, which is the summation of the three HRD signatures: HRD-LOH, the number of regions with a loss >15 Mbp but shorter than the whole chromosome; TAI, the number of regions of gain and loss >10Mbp that extend to a subtelomere but do not cross the centromere; and LST, the number of chromosomal breakpoints whose SV size >10Mb but not the whole chromosome. We applied this novel algorithm to 20 samples from solid tumors and myeloid neoplasms, and the automated scores are concordant with expertly curated scores on the same OGM data. Further, compared with NGS or CMA, OGM data analyzed with this automated algorithm is able to detect many more HRD related variant compared to other approaches. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 22107762
- Volume :
- 278
- Database :
- Academic Search Index
- Journal :
- Cancer Genetics
- Publication Type :
- Academic Journal
- Accession number :
- 173342307
- Full Text :
- https://doi.org/10.1016/j.cancergen.2023.08.011