48. Utility of whole genome optical mapping (WGOM) in cytogenetic analysis of solid tumors and hematologic malignancies (HM)

      Structural variation (SV) detection is essential for prognostication of cancer patients. However, karyotype/FISH and microarrays are required to obtain a comprehensive molecular profile. Although next-generation sequencing has revolutionized cancer genomics, their short read approach limits the detection of several SVs. The Bionano-WGOM technology, which images ultra-long DNA-molecules demonstrates the potential to replace these conventional techniques for detecting SVs. In pilot investigation on twenty cases previously characterized by conventional techniques, HM (blood, BMA, frozen BMNCs) and solid tumors (frozen tissue) were analyzed on Bionano Saphyr platform. WGOM, in addition to identifying previously characterized SVs, demonstrated a higher resolution and sensitivity to accurately define SVs w.r.t size and location. The following variant types were validated: monosomy, deletions, duplications, insertions, inversion, and translocations. In MDS and CML cases with <5% blasts, WGOM identified t(3;17),-7 and t(9;22)(q34;q11) BCR/ABL1, respectively. Similarly, in the case of glioblastoma, WGOM identified 1p/19q deletion in the sample that previously required micro-dissection for analysis on microarray. WGOM was able to accurately localize with specific coordinates of the marker- and ring- chromosomes originally observed by karyotyping. WGOM was able to confirm the changes in CNVs with simultaneous detection of duplication, deletion and/or translocation on the observed locations. In addition, several novel findings of clinical significance were identified, which are being validated. We anticipate that this approach of obtaining high-resolution genomic data at reduced cost will facilitate in more precise diagnosis and better prognostication of malignancies which was not previously possible.
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