Abstract | INTRODUCTION: METHODS:
Chromosomal aberrations and chromothripsis were detected by methylation-based copy number variation (CNV) analysis, whereas TMB and MSI were calculated based on large next-generation sequencing (NGS) panels. Putative primaries were assigned by consensus between two independent oncologists. RESULTS: CNV losses varied depending on putative primaries and were more abundant in patients harboring TP53 mutations and/or deletions 17p. CNV loss was prognostically adverse in localized CUP treated with surgery and/or radiotherapy, but not in disseminated poor-risk CUP treated with palliative chemotherapy. CNV loss also worsened the prognosis in squamous cell CUP. Chromothripsis was detected in 18/59 (30.5%) patients without prognostic effect. TMB was highest in cases with MSI, squamous cell histology, and with lung, anal or cervical putative primaries. CONCLUSION: Overall, CNV, chromothripsis, TMB, and MSI profiles in CUP are reminiscent of biological characteristics known from other cancer entities without a unifying CUP-specific signature. Markedly, high-level CNV loss is an adverse predictive biomarker in localized but not disseminated chemotherapy-treated CUP. This implies that chromosomal losses drive CUP progression, but also increase susceptibility to chemotherapy, with both effects apparently leveling out in disseminated CUP.
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Authors | Tilmann Bochtler, Timothy Wohlfromm, Thomas Hielscher, Damian Stichel, Maria Pouyiourou, Bianca Kraft, Olaf Neumann, Volker Endris, Andreas von Deimling, Albrecht Stenzinger, Alwin Krämer |
Journal | Genes, chromosomes & cancer
(Genes Chromosomes Cancer)
Vol. 61
Issue 9
Pg. 551-560
(09 2022)
ISSN: 1098-2264 [Electronic] United States |
PMID | 35430765
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2022 The Authors. Genes, Chromosomes and Cancer published by Wiley Periodicals LLC. |
Chemical References |
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Topics |
- Biomarkers, Tumor
(genetics)
- Carcinoma
- Chromosome Aberrations
- Chromothripsis
- DNA Copy Number Variations
- Humans
- Microsatellite Instability
- Mutation
- Neoplasms, Unknown Primary
(genetics)
- Prognosis
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