Evolutionary characterization of lung adenocarcinoma morphology in TRACERx
In: Evolutionary characterization of lung adenocarcinoma morphology in TRACERx. Karasaki, T. and Moore, D.A. and Veeriah, 2023
academicJournal
Zugriff:
Lung adenocarcinomas (LUADs) display a broad histological spectrum from low-grade lepidic tumors through to mid-grade acinar and papillary and high-grade solid, cribriform and micropapillary tumors. How morphology reflects tumor evolution and disease progression is poorly understood. Whole-exome sequencing data generated from 805 primary tumor regions and 121 paired metastatic samples across 248 LUADs from the TRACERx 421 cohort, together with RNA-sequencing data from 463 primary tumor regions, were integrated with detailed whole-tumor and regional histopathological analysis. Tumors with predominantly high-grade patterns showed increased chromosomal complexity, with higher burden of loss of heterozygosity and subclonal somatic copy number alterations. Individual regions in predominantly high-grade pattern tumors exhibited higher proliferation and lower clonal diversity, potentially reflecting large recent subclonal expansions. Co-occurrence of truncal loss of chromosomes 3p and 3q was enriched in predominantly low-/mid-grade tumors, while purely undifferentiated solid-pattern tumors had a higher frequency of truncal arm or focal 3q gains and SMARCA4 gene alterations compared with mixed-pattern tumors with a solid component, suggesting distinct evolutionary trajectories. Clonal evolution analysis revealed that tumors tend to evolve toward higher-grade patterns. The presence of micropapillary pattern and 'tumor spread through air spaces' were associated with intrathoracic recurrence, in contrast to the presence of solid/cribriform patterns, necrosis and preoperative circulating tumor DNA detection, which were associated with extra-thoracic recurrence. These data provide insights into the relationship between LUAD morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk.
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Evolutionary characterization of lung adenocarcinoma morphology in TRACERx
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Autor/in / Beteiligte Person: | Karasaki, T. ; Moore, D.A. ; Veeriah, S. ; Naceur-Lombardelli, C. ; Toncheva, A. ; Magno, N. ; Ward, S. ; Bakir, M.A. ; Watkins, T.B.K. ; Grigoriadis, K. ; Huebner, A. ; Hill, M.S. ; Frankell, A.M. ; Abbosh, C. ; Puttick, C. ; Zhai, H. ; Gimeno-Valiente, F. ; Saghafinia, S. ; Kanu, N. ; Dietzen, M. ; Pich, O. ; Lim, E. ; Martínez-Ruiz, C. ; Black, J.R.M. ; Biswas, D. ; Campbell, B.B. ; Lee, C. ; Colliver, E. ; Enfield, K.S.S. ; Hessey, S. ; Hiley, C.T. ; Zaccaria, S. ; Litchfield, K. ; Birkbak, N.J. ; Cadieux, E.L. ; Demeulemeester, J. ; Van Loo, P. ; Adusumilli, P.S. ; Tan, K.S. ; Cheema, W. ; Sanchez-Vega, F. ; Jones, D.R. ; Rekhtman, N. ; Travis, W.D. ; Hackshaw, A. ; Marafioti, T. ; Salgado, R. ; Le Quesne, J. ; Nicholson, A.G. ; McGranahan, N. ; Swanton, C. ; Jamal-Hanjani, M. |
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Zeitschrift: | Evolutionary characterization of lung adenocarcinoma morphology in TRACERx. Karasaki, T. and Moore, D.A. and Veeriah, 2023 |
Veröffentlichung: | Nature Publishing Group, 2023 |
Medientyp: | academicJournal |
DOI: | 10.1038/s41591-023-02230-w |
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