Tracking the Evolution of Non–Small-Cell Lung Cancer

Jamal‐Hanjani, Mariam; Wilson, Gareth A.; McGranahan, Nicholas; Birkbak, Nicolai J.; Watkins, Thomas B.K.; Veeriah, Selvaraju; Shafi, Seema; Johnson, Diana; Mitter, Richard; Rosenthal, Rachel; Salm, Max; Horswell, Stuart; Escudero, Mickael; Matthews, Nik; Rowan, Andrew; Chambers, Tim; Moore, David A.; Turajlic, Samra; Xu, Hang; Lee, Siow Ming; Förster, Martin; Ahmad, Tanya; Hiley, Crispin; Abbosh, Christopher; Falzon, Mary; Borg, Elaine; Marafioti, Teresa; Lawrence, David; Hayward, Martin; Kolvekar, Shyam; Παναγιωτόπουλος, Νικόλαος; Janes, Sam M.; Thakrar, Ricky; Ahmed, Asia; Blackhall, Fiona; Summers, Yvonne; Shah, Rajesh; Joseph, Leena Dennis; Quinn, Anne Marie; Crosbie, Philip; Naidu, Babu; Middleton, Gary; Langman, Gerald; Trotter, Simon; Nicolson, Marianne; Remmen, Hardy; Kerr, Keith M.; Chetty, Mahendran; Gomersall, Lesley; Fennell, Dean A.; Nakas, Apostolos; Rathinam, Sridhar; Anand, Girija; Khan, Sajid; Russell, Peter; Ezhil, Veni; Ismail, Babikir; Irvin-Sellers, Melanie; Prakash, Vineet; Lester, J.F.; Kornaszewska, Malgorzata; Attanoos, Richard; Adams, Haydn; Davies, Helen; Dentro, Stefan C.; Tanière, Philippe; O’Sullivan, B.; Lowe, Helen; Hartley, John A.; Iles, Natasha; Bell, Harriet; Ngai, Yenting; Shaw, Jacqui A.; Herrero, Javier; Szállási, Zoltán; Schwarz, Roland F.; Stewart, Aengus; Quezada, Sergio A.; Quesne, John Le; Loo, Peter Van; Dive, Caroline; Hackshaw, Allan; Swanton, Charles

doi:10.1056/nejmoa1616288

Cited by 1,943 publications

(2,134 citation statements)

References 29 publications

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“…We attempted cell culture from 12 patients (median age = 75 years, range = 58–90 years), whose surgically resected primary lung adenocarcinoma (LUAD) tumors (stage II [ n = 9] or III [ n = 3]) are being analyzed in the on‐going Tracking Cancer Evolution through Therapy (TRACERx) clinical study,14, 15 using a published protocol 17. We obtained primary epithelial cell cultures that could be passaged from 10 (83.3%) of these.…”

Section: Resultsmentioning

confidence: 99%

“…Here, we present cell culture outcomes for 12 lung adenocarcinoma patients enrolled in the on‐going Tracking Cancer Evolution through Therapy (TRACERx) clinical study 14, 15. We found that contaminating normal epithelial cells were the predominant cell type present in early passage cultures, although tumor cells were cultured in one case.…”

Section: Introductionmentioning

confidence: 99%

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Expansion of airway basal epithelial cells from primary human non‐small cell lung cancer tumors

Hynds

Aissa

Gowers

et al. 2018

Intl Journal of Cancer

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Pre‐clinical non‐small cell lung cancer (NSCLC) models are poorly representative of the considerable inter‐ and intra‐tumor heterogeneity of the disease in patients. Primary cell‐based in vitro models of NSCLC are therefore desirable for novel therapy development and personalized cancer medicine. Methods have been described to generate rapidly proliferating epithelial cell cultures from multiple human epithelia using 3T3‐J2 feeder cell culture in the presence of Y‐27632, a RHO‐associated protein kinase (ROCK) inhibitor, in what are known as “conditional reprograming conditions” (CRC) or 3T3 + Y. In some cancer studies, variations of this methodology have allowed primary tumor cell expansion across a number of cancer types but other studies have demonstrated the preferential expansion of normal epithelial cells from tumors in such conditions. Here, we report our experience regarding the derivation of primary NSCLC cell cultures from 12 lung adenocarcinoma patients enrolled in the Tracking Cancer Evolution through Therapy (TRACERx) clinical study and discuss these in the context of improving the success rate for in vitro cultivation of cells from NSCLC tumors.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Expansion of airway basal epithelial cells from primary human non‐small cell lung cancer tumors

Hynds

Aissa

Gowers

et al. 2018

Intl Journal of Cancer

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“…To prospectively investigate ITH in relation to clinical outcome and to determine the clonal nature of driver events and evolutionary processes in early‐stage NSCLC, Jamal‐Hanjani et al22 sequenced 327 tumor regions and 100 matched germline samples derived from whole blood. These data may have important implications for understanding tumor biology and therapeutic control in NSCLC.…”

Section: Further Analysis Of Ith For Clinical Applicationsmentioning

confidence: 99%

“…1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 This multiregional analysis (MRA) sequencing approach enabled us not only to observe spatial heterogeneity, but also to calculate temporal alterations and eventually disclose the evolution of tumors. There are two types of somatic aberration in a tumor: ubiquitous aberrations (founder mutations, trunk mutations, or clonal mutations) and scattered aberrations (progressor mutations, branch/leaf mutations, or subclonal mutations).…”

Section: Introductionmentioning

confidence: 99%

Cancer evolution and heterogeneity

Mimori

Saito

Niida

et al. 2018

Annals of Gastroent Surgery

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Undoubtedly, intratumor heterogeneity (ITH) is one of the causes of the intractability of cancers. Recently, technological innovation in genomics has promoted studies on ITH in solid tumors and on the pattern and level of diversity, which varies among malignancies. We profiled the genome in multiple regions of nine colorectal cancer (CRC) cases. The most impressive finding was that in the late phase, a parental clone branched into numerous subclones. We found that minor mutations were dominant in advanced CRC named neutral evolution; that is, driver gene aberrations were observed with high proportion in the early‐acquired phase, but low in the late‐acquired phase. Then, we validated that neutral evolution could cause ITH in advanced CRC by super‐computational analysis. According to the clinical findings, we explored a branching evolutionary process model in cancer evolution, which assumes that each tumor cell has cellular automaton. According to the model, we verified factors to foster ITH with neutral evolution in advanced CRC. In this review, we introduce recent advances in the field of ITH including the general component of ITH, clonal selective factors that consolidate the evolutionary process, and a representative clinical application of ITH.

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“…Swanton and colleagues have reported preliminary results of the whole-exome sequencing of 100 early-stage NSCLC in order to correlate the heterogeneity towards the study of clonal and subclonal events to meaningful clinical outcome named recurrence-free survival (5).…”

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confidence: 99%