Journal Article

DKFZ-2022-00750

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Prognostic Impact of Copy Number Alterations and Tumor Mutational Burden in Carcinoma of Unknown Primary.

Bochtler, T. (First author)DKFZ* ; Wohlfromm, T.DKFZ* ; Hielscher, T.DKFZ* ; Stichel, D.DKFZ* ; Pouyiourou, M.DKFZ* ; Kraft, B.DKFZ* ; Neumann, O. ; Endris, V. ; von Deimling, A.DKFZ* ; Stenzinger, A. ; Krämer, A. (Last author)DKFZ*

2022
Wiley-Liss New York, NY

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Please use a persistent id in citations: doi:10.1002/gcc.23047

Abstract: Chromosomal aberrations are known to drive metastatic spread, but their profile is still elusive in carcinoma of unknown primary (CUP). Therefore, it was the aim of this study to characterize the chromosomal aberration pattern in CUP depending on histological and clinical features and to assess its prognostic impact together with chromothripsis, tumor mutational burden (TMB), microsatellite instability (MSI) and mutational profiles as potential prognostic biomarkers.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.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 microsatellite instability, squamous cell histology and with lung, anal or cervical putative primaries.Overall, CNV, chromothripsis, TMB and MSI profiles in CUP are reminescent 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.

Keyword(s): Carcinoma of unknown primary (CUP) ; chromosomal instability ; chromothripsis ; copy number variations (CNV) ; mutational profile ; prognosis ; tumor mutational burden (TMB)

Note: #EA:A360#LA:A360# / 2022 Sep;61(9):551-560

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Contributing Institute(s):

1. KKE Mol. Hämatologie/Onkologie (A360)
2. C060 Biostatistik (C060)
3. KKE Neuropathologie (B300)

Research Program(s):

1. 311 - Zellbiologie und Tumorbiologie (POF4-311) (POF4-311)

Appears in the scientific report 2022

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; Essential Science Indicators ; IF < 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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