@article{8741353,
  abstract     = {{Copy number alterations (CNAs) have increasingly become part of the diagnostic algorithm of glial tumors. Alterations such as homozygous deletion of CDKN2A/B, 7 +/ 10 - chromosome copy number changes or EGFR amplification are predictive of a poor prognosis. The codeletion of chromosome arms 1p and 19q, typically associated with oligodendroglioma, implies a more favorable prognosis. Detection of this codeletion by the current diagnostic standard, being fluorescence in situ hybridization (FISH), is sometimes however subject to technical and interpretation problems. In this study, we evaluated CNA detection by shallow whole-genome sequencing (sWGS) as an inexpensive, complementary molecular technique. A cohort of 36 glioma tissue samples, enriched with "difficult" and "ambiguous" cases, was analyzed by sWGS. sWGS results were compared with FISH assays of chromosomes 1p and 19q. In addition, CNAs relevant to glioblastoma diagnosis were explored. In 4/36 samples, EGFR (7p11.2) amplifications and homozygous loss of CDKN2A/B were identified by sWGS. Six out of 8 IDH-wild-type glioblastomas demonstrated a prognostic chromosome 7/chromosome 10 signature. In 11/36 samples, local interstitial and terminal 1p/19q alterations were detected by sWGS, implying that FISH's targeted nature might promote false arm-level extrapolations. In this cohort, differences in overall survival between patients with and without codeletion were better pronounced by the sequencing-based distinction (likelihood ratio of 7.48) in comparison to FISH groupings (likelihood ratio of 0.97 at diagnosis and 1.79 +/- 0.62 at reobservation), suggesting sWGS is more accurate than FISH. We recognized adverse effects of tissue block age on FISH signals. In addition, we show how sWGS reveals relevant aberrations beyond the 1p/19q state, such as EGFR amplification, combined gain of chromosome 7 and loss of chromosome 10, and homozygous loss of CDKN2A/B. The findings presented by this study might stimulate implementation of sWGS as a complementary, easy to apply technique for copy number detection.}},
  author       = {{Van der Eecken, Kim and Van der Linden, Malaïka and Raman, Lennart and Creytens, David and Dedeurwaerdere, Franceska and De Winne, Koen and Ferdinande, Liesbeth and Lammens, Martin and Menten, Björn and Rottiers, Isabelle and Van Gaever, Bram and Van den Broecke, Caroline and Van de Vijver, Koen and Van Roy, Nadine and Verbeke, Sofie and Van Dorpe, Jo}},
  issn         = {{0945-6317}},
  journal      = {{VIRCHOWS ARCHIV}},
  keywords     = {{Cell Biology,Molecular Biology,General Medicine,Pathology and Forensic Medicine,Copy number aberration detection,Fluorescence in situ hybridization,Glial tumors,Shallow whole-genome sequencing,1p,19q codeletion,IN-SITU HYBRIDIZATION,OLIGODENDROGLIAL TUMORS,DELETION-ANALYSIS,19Q,1P,DIAGNOSIS,PATHOLOGY,LOSSES}},
  language     = {{eng}},
  pages        = {{677--686}},
  title        = {{Shallow whole-genome sequencing : a useful, easy to apply molecular technique for CNA detection on FFPE tumor tissue : a glioma-driven study}},
  url          = {{http://doi.org/10.1007/s00428-022-03268-w}},
  volume       = {{480}},
  year         = {{2022}},
}

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