The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.
Integrative genomic profiling of large-cell neuroendocrine carcinomas reveals distinct subtypes of high-grade neuroendocrine lung tumors
Open accessAbstract
Pulmonary large-cell neuroendocrine carcinomas (LCNECs) have similarities with other lung cancers, but their precise relationship has remained unclear. Here we perform a comprehensive genomic (n = 60) and transcriptomic (n = 69) analysis of 75 LCNECs and identify two molecular subgroups: “type I LCNECs” with bi-allelic TP53 and STK11/KEAP1 alterations (37%), and “type II LCNECs” enriched for bi-allelic inactivation of TP53 and RB1 (42%). Despite sharing genomic alterations with adenocarcinomas and squamous cell carcinomas, no transcriptional relationship was found; instead LCNECs form distinct transcriptional subgroups with closest similarity to SCLC. While type I LCNECs and SCLCs exhibit a neuroendocrine profile with ASCL1high/DLL3high/NOTCHlow, type II LCNECs bear TP53 and RB1 alterations and differ from most SCLC tumors with reduced neuroendocrine markers, a pattern of ASCL1low/DLL3low/NOTCHhigh, and an upregulation of immune-related pathways. In conclusion, LCNECs comprise two molecularly defined subgroups, and distinguishing them from SCLC may allow stratified targeted treatment of high-grade neuroendocrine lung tumors.
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Cited by
Rindi, G., Klimstra, D. S., Abedi-Ardekani, B., Asa, S. L., Bosman, F. T., Brambilla, E., Busam, K. J., de Krijger, R. R., Dietel, M., El-Naggar, A. K., et al. (2018) · Modern Pathology · doi:10.1038/s41379-018-0110-y · Cited by 1,163
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Metadata
- Authors
- George, J., Walter, V., Peifer, M., Alexandrov, L. B., Seidel, D., Leenders, F., Maas, L., Müller, C., Dahmen, I., Delhomme, T. M., Ardin, M., Leblay, N., Byrnes, G., Sun, R., De Reynies, A., McLeer-Florin, A., Bosco, G., Malchers, F., Menon, R., Altmüller, J., Becker, C., Nürnberg, P., Achter, V., Lang, U., Schneider, P. M., Bogus, M., Soloway, M. G., Wilkerson, M. D., Cun, Y., McKay, J. D., Moro-Sibilot, D., Brambilla, C. G., Lantuejoul, S., Lemaitre, N., Soltermann, A., Weder, W., Tischler, V., Brustugun, O. T., Lund-Iversen, M., Helland, Å., Solberg, S., Ansén, S., Wright, G., Solomon, B., Roz, L., Pastorino, U., Petersen, I., Clement, J. H., Sänger, J., Wolf, J., Vingron, M., Zander, T., Perner, S., Travis, W. D., Haas, S. A., Olivier, M., Foll, M., Büttner, R., Hayes, D. N., Brambilla, E., Fernandez-Cuesta, L., & Thomas, R. K.
- Venue
- Nature Communications
- Published
- 2018-03-13
- Volume
- 9
- Issue
- 1
- Pages
- 1048-1048
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2792828274
- Cited by
- 377
- References
- 13
- FWCI
- 12.55
- Type
- journal article
- Language
- en
- Open access
- gold
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- George, J., Walter, V., Peifer, M., Alexandrov, L. B., Seidel, D., Leenders, F., Maas, L., Müller, C., Dahmen, I., Delhomme, T. M., Ardin, M., Leblay, N., Byrnes, G., Sun, R., De Reynies, A., McLeer-Florin, A., Bosco, G., Malchers, F., Menon, R., . . . Thomas, R. K. (2018). Integrative genomic profiling of large-cell neuroendocrine carcinomas reveals distinct subtypes of high-grade neuroendocrine lung tumors. Nature Communications. https://doi.org/10.1038/s41467-018-03099-x
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