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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© 2020 Published by Elsevier Inc.