PMID- 35034191 OWN - NLM STAT- MEDLINE DCOM- 20220411 LR - 20220728 IS - 1432-2307 (Electronic) IS - 0945-6317 (Linking) VI - 480 IP - 3 DP - 2022 Mar TI - Shallow whole-genome sequencing: a useful, easy to apply molecular technique for CNA detection on FFPE tumor tissue-a glioma-driven study. PG - 677-686 LID - 10.1007/s00428-022-03268-w [doi] AB - 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. CI - (c) 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Van der Eecken, Kim AU - Van der Eecken K AD - Department of Pathology, Ghent University, Ghent University Hospital, Ghent, Belgium. AD - Cancer Research Institute (CRIG), Ghent, Belgium. FAU - Van der Linden, Malaika AU - Van der Linden M AD - Department of Pathology, Ghent University, Ghent University Hospital, Ghent, Belgium. AD - Cancer Research Institute (CRIG), Ghent, Belgium. AD - Center for Medical Genetics, Department of Biomolecular Medicine, Ghent University, Ghent University Hospital, Ghent, Belgium. FAU - Raman, Lennart AU - Raman L AD - Department of Pathology, Ghent University, Ghent University Hospital, Ghent, Belgium. AD - Center for Medical Genetics, Department of Biomolecular Medicine, Ghent University, Ghent University Hospital, Ghent, Belgium. FAU - Creytens, David AU - Creytens D AD - Department of Pathology, Ghent University, Ghent University Hospital, Ghent, Belgium. AD - Cancer Research Institute (CRIG), Ghent, Belgium. FAU - Dedeurwaerdere, Franceska AU - Dedeurwaerdere F AD - Department of Pathology, AZ Delta, Roeselare, Belgium. FAU - De Winne, Koen AU - De Winne K AD - Department of Pathology, Antwerp University Hospital, Antwerp, Belgium. FAU - Ferdinande, Liesbeth AU - Ferdinande L AD - Department of Pathology, Ghent University, Ghent University Hospital, Ghent, Belgium. AD - Cancer Research Institute (CRIG), Ghent, Belgium. FAU - Lammens, Martin AU - Lammens M AD - Department of Pathology, Antwerp University Hospital, Antwerp, Belgium. FAU - Menten, Bjorn AU - Menten B AD - Cancer Research Institute (CRIG), Ghent, Belgium. AD - Center for Medical Genetics, Department of Biomolecular Medicine, Ghent University, Ghent University Hospital, Ghent, Belgium. FAU - Rottiers, Isabelle AU - Rottiers I AD - Department of Pathology, Ghent University, Ghent University Hospital, Ghent, Belgium. AD - Cancer Research Institute (CRIG), Ghent, Belgium. FAU - Van Gaever, Bram AU - Van Gaever B AD - Department of Pathology, Ghent University, Ghent University Hospital, Ghent, Belgium. FAU - Van den Broecke, Caroline AU - Van den Broecke C AD - Department of Pathology, AZ Sint-Lucas, Ghent, Belgium. FAU - Van de Vijver, Koen AU - Van de Vijver K AD - Department of Pathology, Ghent University, Ghent University Hospital, Ghent, Belgium. AD - Cancer Research Institute (CRIG), Ghent, Belgium. FAU - Van Roy, Nadine AU - Van Roy N AD - Cancer Research Institute (CRIG), Ghent, Belgium. AD - Center for Medical Genetics, Department of Biomolecular Medicine, Ghent University, Ghent University Hospital, Ghent, Belgium. FAU - Verbeke, Sofie AU - Verbeke S AD - Department of Pathology, Ghent University, Ghent University Hospital, Ghent, Belgium. AD - Cancer Research Institute (CRIG), Ghent, Belgium. FAU - Van Dorpe, Jo AU - Van Dorpe J AD - Department of Pathology, Ghent University, Ghent University Hospital, Ghent, Belgium. jo.vandorpe@uzgent.be. AD - Cancer Research Institute (CRIG), Ghent, Belgium. jo.vandorpe@uzgent.be. LA - eng GR - BOF.STA.2017.0002.01/Bijzonder Onderzoeksfonds/ PT - Journal Article DEP - 20220116 PL - Germany TA - Virchows Arch JT - Virchows Archiv : an international journal of pathology JID - 9423843 RN - EC 1.1.1.41 (Isocitrate Dehydrogenase) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM MH - *Brain Neoplasms/diagnosis/genetics/pathology MH - Chromosome Deletion MH - Chromosomes, Human, Pair 19 MH - ErbB Receptors/genetics MH - *Glioma/diagnosis/genetics/pathology MH - Homozygote MH - Humans MH - In Situ Hybridization, Fluorescence/methods MH - Isocitrate Dehydrogenase/genetics MH - Sequence Deletion OTO - NOTNLM OT - 1p/19q codeletion OT - Copy number aberration detection OT - Fluorescence in situ hybridization OT - Glial tumors OT - Shallow whole-genome sequencing EDAT- 2022/01/17 06:00 MHDA- 2022/04/12 06:00 CRDT- 2022/01/16 21:15 PHST- 2021/08/16 00:00 [received] PHST- 2022/01/03 00:00 [accepted] PHST- 2021/12/10 00:00 [revised] PHST- 2022/01/17 06:00 [pubmed] PHST- 2022/04/12 06:00 [medline] PHST- 2022/01/16 21:15 [entrez] AID - 10.1007/s00428-022-03268-w [pii] AID - 10.1007/s00428-022-03268-w [doi] PST - ppublish SO - Virchows Arch. 2022 Mar;480(3):677-686. doi: 10.1007/s00428-022-03268-w. Epub 2022 Jan 16.