Evolutionary characterization of lung adenocarcinoma morphology in TRACERx
© 2023. The Author(s) under exclusive license to Springer Nature America, Inc..
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.
| Errataetall: | |
|---|---|
| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:29 |
|---|---|
| Enthalten in: |
Nature medicine - 29(2023), 4 vom: 12. Apr., Seite 833-845 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Karasaki, Takahiro [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 21.04.2023 Date Revised 20.03.2024 published: Print-Electronic CommentIn: Nat Med. 2023 Apr;29(4):795-796. - PMID 37045998 Citation Status MEDLINE |
|---|
| doi: |
10.1038/s41591-023-02230-w |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM35550362X |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM35550362X | ||
| 003 | DE-627 | ||
| 005 | 20240320233053.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41591-023-02230-w |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1337.xml |
| 035 | |a (DE-627)NLM35550362X | ||
| 035 | |a (NLM)37045996 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Karasaki, Takahiro |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Evolutionary characterization of lung adenocarcinoma morphology in TRACERx |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 21.04.2023 | ||
| 500 | |a Date Revised 20.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a CommentIn: Nat Med. 2023 Apr;29(4):795-796. - PMID 37045998 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023. The Author(s) under exclusive license to Springer Nature America, Inc. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a SMARCA4 protein, human |2 NLM | |
| 650 | 7 | |a EC 3.6.1.- |2 NLM | |
| 650 | 7 | |a DNA Helicases |2 NLM | |
| 650 | 7 | |a EC 3.6.4.- |2 NLM | |
| 650 | 7 | |a Nuclear Proteins |2 NLM | |
| 650 | 7 | |a Transcription Factors |2 NLM | |
| 700 | 1 | |a Moore, David A |e verfasserin |4 aut | |
| 700 | 1 | |a Veeriah, Selvaraju |e verfasserin |4 aut | |
| 700 | 1 | |a Naceur-Lombardelli, Cristina |e verfasserin |4 aut | |
| 700 | 1 | |a Toncheva, Antonia |e verfasserin |4 aut | |
| 700 | 1 | |a Magno, Neil |e verfasserin |4 aut | |
| 700 | 1 | |a Ward, Sophia |e verfasserin |4 aut | |
| 700 | 1 | |a Bakir, Maise Al |e verfasserin |4 aut | |
| 700 | 1 | |a Watkins, Thomas B K |e verfasserin |4 aut | |
| 700 | 1 | |a Grigoriadis, Kristiana |e verfasserin |4 aut | |
| 700 | 1 | |a Huebner, Ariana |e verfasserin |4 aut | |
| 700 | 1 | |a Hill, Mark S |e verfasserin |4 aut | |
| 700 | 1 | |a Frankell, Alexander M |e verfasserin |4 aut | |
| 700 | 1 | |a Abbosh, Christopher |e verfasserin |4 aut | |
| 700 | 1 | |a Puttick, Clare |e verfasserin |4 aut | |
| 700 | 1 | |a Zhai, Haoran |e verfasserin |4 aut | |
| 700 | 1 | |a Gimeno-Valiente, Francisco |e verfasserin |4 aut | |
| 700 | 1 | |a Saghafinia, Sadegh |e verfasserin |4 aut | |
| 700 | 1 | |a Kanu, Nnennaya |e verfasserin |4 aut | |
| 700 | 1 | |a Dietzen, Michelle |e verfasserin |4 aut | |
| 700 | 1 | |a Pich, Oriol |e verfasserin |4 aut | |
| 700 | 1 | |a Lim, Emilia L |e verfasserin |4 aut | |
| 700 | 1 | |a Martínez-Ruiz, Carlos |e verfasserin |4 aut | |
| 700 | 1 | |a Black, James R M |e verfasserin |4 aut | |
| 700 | 1 | |a Biswas, Dhruva |e verfasserin |4 aut | |
| 700 | 1 | |a Campbell, Brittany B |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Claudia |e verfasserin |4 aut | |
| 700 | 1 | |a Colliver, Emma |e verfasserin |4 aut | |
| 700 | 1 | |a Enfield, Katey S S |e verfasserin |4 aut | |
| 700 | 1 | |a Hessey, Sonya |e verfasserin |4 aut | |
| 700 | 1 | |a Hiley, Crispin T |e verfasserin |4 aut | |
| 700 | 1 | |a Zaccaria, Simone |e verfasserin |4 aut | |
| 700 | 1 | |a Litchfield, Kevin |e verfasserin |4 aut | |
| 700 | 1 | |a Birkbak, Nicolai J |e verfasserin |4 aut | |
| 700 | 1 | |a Cadieux, Elizabeth Larose |e verfasserin |4 aut | |
| 700 | 1 | |a Demeulemeester, Jonas |e verfasserin |4 aut | |
| 700 | 1 | |a Van Loo, Peter |e verfasserin |4 aut | |
| 700 | 1 | |a Adusumilli, Prasad S |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Kay See |e verfasserin |4 aut | |
| 700 | 1 | |a Cheema, Waseem |e verfasserin |4 aut | |
| 700 | 1 | |a Sanchez-Vega, Francisco |e verfasserin |4 aut | |
| 700 | 1 | |a Jones, David R |e verfasserin |4 aut | |
| 700 | 1 | |a Rekhtman, Natasha |e verfasserin |4 aut | |
| 700 | 1 | |a Travis, William D |e verfasserin |4 aut | |
| 700 | 1 | |a Hackshaw, Allan |e verfasserin |4 aut | |
| 700 | 1 | |a Marafioti, Teresa |e verfasserin |4 aut | |
| 700 | 1 | |a Salgado, Roberto |e verfasserin |4 aut | |
| 700 | 1 | |a Le Quesne, John |e verfasserin |4 aut | |
| 700 | 1 | |a Nicholson, Andrew G |e verfasserin |4 aut | |
| 700 | 0 | |a TRACERx Consortium |e verfasserin |4 aut | |
| 700 | 1 | |a McGranahan, Nicholas |e verfasserin |4 aut | |
| 700 | 1 | |a Swanton, Charles |e verfasserin |4 aut | |
| 700 | 1 | |a Jamal-Hanjani, Mariam |e verfasserin |4 aut | |
| 700 | 1 | |a Van Loo, Peter |e investigator |4 oth | |
| 700 | 1 | |a Le Quesne, John |e investigator |4 oth | |
| 700 | 1 | |a Lester, Jason F |e investigator |4 oth | |
| 700 | 1 | |a Bajaj, Amrita |e investigator |4 oth | |
| 700 | 1 | |a Nakas, Apostolos |e investigator |4 oth | |
| 700 | 1 | |a Sodha-Ramdeen, Azmina |e investigator |4 oth | |
| 700 | 1 | |a Ang, Keng |e investigator |4 oth | |
| 700 | 1 | |a Tufail, Mohamad |e investigator |4 oth | |
| 700 | 1 | |a Chowdhry, Mohammed Fiyaz |e investigator |4 oth | |
| 700 | 1 | |a Scotland, Molly |e investigator |4 oth | |
| 700 | 1 | |a Boyles, Rebecca |e investigator |4 oth | |
| 700 | 1 | |a Rathinam, Sridhar |e investigator |4 oth | |
| 700 | 1 | |a Wilson, Claire |e investigator |4 oth | |
| 700 | 1 | |a Marrone, Domenic |e investigator |4 oth | |
| 700 | 1 | |a Dulloo, Sean |e investigator |4 oth | |
| 700 | 1 | |a Fennell, Dean A |e investigator |4 oth | |
| 700 | 1 | |a Matharu, Gurdeep |e investigator |4 oth | |
| 700 | 1 | |a Shaw, Jacqui A |e investigator |4 oth | |
| 700 | 1 | |a Riley, Joan |e investigator |4 oth | |
| 700 | 1 | |a Primrose, Lindsay |e investigator |4 oth | |
| 700 | 1 | |a Boleti, Ekaterini |e investigator |4 oth | |
| 700 | 1 | |a Cheyne, Heather |e investigator |4 oth | |
| 700 | 1 | |a Khalil, Mohammed |e investigator |4 oth | |
| 700 | 1 | |a Richardson, Shirley |e investigator |4 oth | |
| 700 | 1 | |a Cruickshank, Tracey |e investigator |4 oth | |
| 700 | 1 | |a Price, Gillian |e investigator |4 oth | |
| 700 | 1 | |a Kerr, Keith M |e investigator |4 oth | |
| 700 | 1 | |a Benafif, Sarah |e investigator |4 oth | |
| 700 | 1 | |a Gilbert, Kayleigh |e investigator |4 oth | |
| 700 | 1 | |a Naidu, Babu |e investigator |4 oth | |
| 700 | 1 | |a Patel, Akshay J |e investigator |4 oth | |
| 700 | 1 | |a Osman, Aya |e investigator |4 oth | |
| 700 | 1 | |a Lacson, Christer |e investigator |4 oth | |
| 700 | 1 | |a Langman, Gerald |e investigator |4 oth | |
| 700 | 1 | |a Shackleford, Helen |e investigator |4 oth | |
| 700 | 1 | |a Djearaman, Madava |e investigator |4 oth | |
| 700 | 1 | |a Kadiri, Salma |e investigator |4 oth | |
| 700 | 1 | |a Middleton, Gary |e investigator |4 oth | |
| 700 | 1 | |a Leek, Angela |e investigator |4 oth | |
| 700 | 1 | |a Hodgkinson, Jack Davies |e investigator |4 oth | |
| 700 | 1 | |a Totten, Nicola |e investigator |4 oth | |
| 700 | 1 | |a Montero, Angeles |e investigator |4 oth | |
| 700 | 1 | |a Smith, Elaine |e investigator |4 oth | |
| 700 | 1 | |a Fontaine, Eustace |e investigator |4 oth | |
| 700 | 1 | |a Granato, Felice |e investigator |4 oth | |
| 700 | 1 | |a Doran, Helen |e investigator |4 oth | |
| 700 | 1 | |a Novasio, Juliette |e investigator |4 oth | |
| 700 | 1 | |a Rammohan, Kendadai |e investigator |4 oth | |
| 700 | 1 | |a Joseph, Leena |e investigator |4 oth | |
| 700 | 1 | |a Bishop, Paul |e investigator |4 oth | |
| 700 | 1 | |a Shah, Rajesh |e investigator |4 oth | |
| 700 | 1 | |a Moss, Stuart |e investigator |4 oth | |
| 700 | 1 | |a Joshi, Vijay |e investigator |4 oth | |
| 700 | 1 | |a Crosbie, Philip |e investigator |4 oth | |
| 700 | 1 | |a Gomes, Fabio |e investigator |4 oth | |
| 700 | 1 | |a Brown, Kate |e investigator |4 oth | |
| 700 | 1 | |a Carter, Mathew |e investigator |4 oth | |
| 700 | 1 | |a Chaturvedi, Anshuman |e investigator |4 oth | |
| 700 | 1 | |a Priest, Lynsey |e investigator |4 oth | |
| 700 | 1 | |a Oliveira, Pedro |e investigator |4 oth | |
| 700 | 1 | |a Lindsay, Colin R |e investigator |4 oth | |
| 700 | 1 | |a Blackhall, Fiona H |e investigator |4 oth | |
| 700 | 1 | |a Krebs, Matthew G |e investigator |4 oth | |
| 700 | 1 | |a Summers, Yvonne |e investigator |4 oth | |
| 700 | 1 | |a Clipson, Alexandra |e investigator |4 oth | |
| 700 | 1 | |a Tugwood, Jonathan |e investigator |4 oth | |
| 700 | 1 | |a Kerr, Alastair |e investigator |4 oth | |
| 700 | 1 | |a Rothwell, Dominic G |e investigator |4 oth | |
| 700 | 1 | |a Kilgour, Elaine |e investigator |4 oth | |
| 700 | 1 | |a Dive, Caroline |e investigator |4 oth | |
| 700 | 1 | |a Aerts, Hugo J W L |e investigator |4 oth | |
| 700 | 1 | |a Schwarz, Roland F |e investigator |4 oth | |
| 700 | 1 | |a Kaufmann, Tom L |e investigator |4 oth | |
| 700 | 1 | |a Wilson, Gareth A |e investigator |4 oth | |
| 700 | 1 | |a Rosenthal, Rachel |e investigator |4 oth | |
| 700 | 1 | |a Szallasi, Zoltan |e investigator |4 oth | |
| 700 | 1 | |a Kisistok, Judit |e investigator |4 oth | |
| 700 | 1 | |a Sokac, Mateo |e investigator |4 oth | |
| 700 | 1 | |a Diossy, Miklos |e investigator |4 oth | |
| 700 | 1 | |a Bunkum, Abigail |e investigator |4 oth | |
| 700 | 1 | |a Stewart, Aengus |e investigator |4 oth | |
| 700 | 1 | |a Magness, Alastair |e investigator |4 oth | |
| 700 | 1 | |a Rowan, Andrew |e investigator |4 oth | |
| 700 | 1 | |a Karamani, Angeliki |e investigator |4 oth | |
| 700 | 1 | |a Chain, Benny |e investigator |4 oth | |
| 700 | 1 | |a Castignani, Carla |e investigator |4 oth | |
| 700 | 1 | |a Bailey, Chris |e investigator |4 oth | |
| 700 | 1 | |a Weeden, Clare E |e investigator |4 oth | |
| 700 | 1 | |a Richard, Corentin |e investigator |4 oth | |
| 700 | 1 | |a Pearce, David R |e investigator |4 oth | |
| 700 | 1 | |a Karagianni, Despoina |e investigator |4 oth | |
| 700 | 1 | |a Levi, Dina |e investigator |4 oth | |
| 700 | 1 | |a Hoxha, Elena |e investigator |4 oth | |
| 700 | 1 | |a Nye, Emma |e investigator |4 oth | |
| 700 | 1 | |a Grönroos, Eva |e investigator |4 oth | |
| 700 | 1 | |a Gálvez-Cancino, Felip |e investigator |4 oth | |
| 700 | 1 | |a Athanasopoulou, Foteini |e investigator |4 oth | |
| 700 | 1 | |a Kassiotis, George |e investigator |4 oth | |
| 700 | 1 | |a Stavrou, Georgia |e investigator |4 oth | |
| 700 | 1 | |a Mastrokalos, Gerasimos |e investigator |4 oth | |
| 773 | 0 | 8 | |i Enthalten in |t Nature medicine |d 1995 |g 29(2023), 4 vom: 12. Apr., Seite 833-845 |w (DE-627)NLM074659804 |x 1546-170X |7 nnns |
| 773 | 1 | 8 | |g volume:29 |g year:2023 |g number:4 |g day:12 |g month:04 |g pages:833-845 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1038/s41591-023-02230-w |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 29 |j 2023 |e 4 |b 12 |c 04 |h 833-845 | ||