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Clinically relevant...
Clinically relevant molecular hallmarks of PFA ependymomas display intratumoral heterogeneity and correlate with tumor morphology
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Goedicke, Swenja (författare)
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Kresbach, Catena (författare)
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Ehlert, Max (författare)
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Obrecht, Denise (författare)
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Altendorf, Lea (författare)
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Hack, Karoline (författare)
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von Hoff, Katja (författare)
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- Carén, Helena, 1979 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för laboratoriemedicin,Department of Laboratory Medicine
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Melcher, Viktoria (författare)
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Kerl, Kornelius (författare)
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Englinger, Bernhard (författare)
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Filbin, Mariella (författare)
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Pajtler, Kristian W. (författare)
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Gojo, Johannes (författare)
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Pietsch, Torsten (författare)
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Rutkowski, Stefan (författare)
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Schueller, Ulrich (författare)
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(creator_code:org_t)
- 2024
- 2024
- Engelska.
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Ingår i: ACTA NEUROPATHOLOGICA. - 0001-6322 .- 1432-0533. ; 147:1
- Relaterad länk:
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Posterior fossa type A (PF-EPN-A, PFA) ependymoma are aggressive tumors that mainly affect children and have a poor prognosis. Histopathology shows significant intratumoral heterogeneity, ranging from loose tissue to often sharply demarcated, extremely cell-dense tumor areas. To determine molecular differences in morphologically different areas and to understand their clinical significance, we analyzed 113 PF-EPN-A samples, including 40 corresponding relapse samples. Cell-dense areas ranged from 0 to 100% of the tumor area and displayed a higher proportion of proliferating tumor cells (p < 0.01). Clinically, cell density was associated with poor progression-free and overall survival (pPFS = 0.0026, pOS < 0.01). Molecularly, tumor areas with low and high cell density showed diverging DNA methylation profiles regarding their similarity to distinct previously discovered PF-EPN-A subtypes in 9/21 cases. Prognostically relevant chromosomal changes at 1q and 6q showed spatial heterogeneity within single tumors and were significantly enriched in cell-dense tumor areas as shown by single-cell RNA (scRNA)-sequencing as well as copy number profiling and fluorescence in situ hybridization (FISH) analyses of different tumor areas. Finally, spatial transcriptomics revealed cell-dense areas of different tumors to be more similar than various different areas of the same tumor. High-density areas distinctly overexpressed genes encoding histone proteins, WNT5A, TGFB1, or IGF2. Relapsing tumors displayed a higher proportion of cell-dense areas (p = 0.036), a change in PF-EPN-A methylation subtypes (13/32 patients), and novel chromosome 1q gains and 6q losses (12/32 cases) compared to corresponding primary tumors. Our data suggest that PF-EPN-A ependymomas habor a previously unrecognized intratumoral heterogeneity with clinical implications, which has to be accounted for when selecting diagnostic material, inter alia, by histological evaluation of the proportion of cell-dense areas.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- Ependymoma
- Intratumoral heterogeneity
- 1q gain
- 6q loss
- Morphology
- DNA methylation
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Goedicke, Swenja
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Kresbach, Catena
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Ehlert, Max
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Obrecht, Denise
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Altendorf, Lea
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Hack, Karoline
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visa fler...
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von Hoff, Katja
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Carén, Helena, 1 ...
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Melcher, Viktori ...
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Kerl, Kornelius
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Englinger, Bernh ...
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Filbin, Mariella
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Pajtler, Kristia ...
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Gojo, Johannes
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Pietsch, Torsten
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Rutkowski, Stefa ...
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Schueller, Ulric ...
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Neurovetenskaper
- Artiklar i publikationen
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ACTA NEUROPATHOL ...
- Av lärosätet
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Göteborgs universitet