The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
NOTCH, ASCL1, p53 and RB alterations define an alternative pathway driving neuroendocrine and small cell lung carcinomas
Open accessAbstract
Small cell lung cancers (SCLCs) and extrapulmonary small cell cancers (SCCs) are very aggressive tumors arising de novo as primary small cell cancer with characteristic genetic lesions in RB1 and TP53. Based on murine models, neuroendocrine stem cells of the terminal bronchioli have been postulated as the cellular origin of primary SCLC. However, both in lung and many other organs, combined small cell/non‐small cell tumors and secondary transitions from non‐small cell carcinomas upon cancer therapy to neuroendocrine and small cell tumors occur. We define features of “small cell‐ness” based on neuroendocrine markers, characteristic RB1 and TP53 mutations and small cell morphology. Furthermore, here we identify a pathway driving the pathogenesis of secondary SCLC involving inactivating NOTCH mutations, activation of the NOTCH target ASCL1 and canonical WNT‐signaling in the context of mutual bi‐allelic RB1 and TP53 lesions. Additionaly, we explored ASCL1 dependent RB inactivation by phosphorylation, which is reversible by CDK5 inhibition. We experimentally verify the NOTCH‐ASCL1‐RB‐p53 signaling axis in vitro and validate its activation by genetic alterations in vivo. We analyzed clinical tumor samples including SCLC, SCC and pulmonary large cell neuroendocrine carcinomas and adenocarcinomas using amplicon‐based Next Generation Sequencing, immunohistochemistry and fluorescence in situ hybridization. In conclusion, we identified a novel pathway underlying rare secondary SCLC which may drive small cell carcinomas in organs other than lung, as well.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Vogelstein, B., Lane, D., & Levine, A. J. (2000) · Nature · doi:10.1038/35042675 · Cited by 6,607
Genotypic and Histological Evolution of Lung Cancers Acquiring Resistance to EGFR Inhibitors
Sequist, L. V., Waltman, B. A., Dias-Santagata, D., Digumarthy, S., Turke, A. B., Fidias, P., Bergethon, K., Shaw, A. T., Gettinger, S., Cosper, A. K., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002003 · Cited by 3,499
Gene-expression profiles predict survival of patients with lung adenocarcinoma
Beer, D. G., Kardia, S. L. R., Huang, C.-C., Giordano, T. J., Levin, A. M., Misek, D. E., Lin, L., Chen, G., Gharib, T. G., Thomas, D. G., et al. (2002) · Nature Medicine · doi:10.1038/nm733 · Cited by 2,025
Cellular mechanisms of tumour suppression by the retinoblastoma gene
Burkhart, D. L., & Sage, J. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2399 · Cited by 974
Meuwissen, R., Linn, S. C., Linnoila, R. I., Zevenhoven, J., Mooi, W. J., & Berns, A. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00220-4 · Cited by 643
Sutherland, K. D., Proost, N., Brouns, I., Adriaensen, D., Song, J.-Y., & Berns, A. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.04.019 · Cited by 534
Coordinated regulation of life and death by RB
Chau, B. N., & Wang, J. Y. J. (2003) · Nature Reviews Cancer · doi:10.1038/nrc993 · Cited by 292
Cited by
Notch signaling pathway: architecture, disease, and therapeutics
Zhou, B., Lin, W., Long, Y., Yang, Y., Zhang, H., Wu, K., & Chu, Q. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00934-y · Cited by 1,114
Small-cell lung cancer: what we know, what we need to know and the path forward
Gazdar, A. F., Bunn, P. A., & Minna, J. D. (2017) · Nature Reviews Cancer · doi:10.1038/nrc.2017.87 · Cited by 904
Lou, Y., Diao, L., Cuentas, E. R. P., Denning, W. L., Chen, L., Fan, Y. H., Byers, L. A., Wang, J., Papadimitrakopoulou, V. A., Behrens, C., et al. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-1434 · Cited by 438
Megyesfalvi, Z., Gay, C. M., Popper, H., Pirker, R., Ostoros, G., Heeke, S., Lang, C., Hoetzenecker, K., Schwendenwein, A., Boettiger, K., et al. (2023) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.21785 · Cited by 369
Delta-like protein 3 expression and therapeutic targeting in neuroendocrine prostate cancer
Puca, L., Gavyert, K., Sailer, V., Conteduca, V., Dardenne, E., Sigouros, M., Isse, K., Kearney, M., Vosoughi, A., Fernandez, L., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aav0891 · Cited by 214
Metadata
- Authors
- Meder, L., König, K., Ozretić, L., Schultheis, A. M., Ueckeroth, F., Ade, C. P., Albus, K., Boehm, D., Rommerscheidt‐Fuss, U., Florin, A., Buhl, T., Hartmann, W., Wolf, J., Merkelbach‐Bruse, S., Eilers, M., Perner, S., Heukamp, L. C., & Buettner, R.
- Venue
- International Journal of Cancer
- Publisher
- Wiley
- Published
- 2015-09-25
- Volume
- 138
- Issue
- 4
- Pages
- 927-938
- ISSN
- 0020-7136 (ISSN-L)
- 1097-0215
- OpenAlex
- W2127327720
- Cited by
- 179
- References
- 7
- FWCI
- 6.24
- Type
- journal article
- Language
- en
- Open access
- hybrid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: NOTCH, ASCL1, p53 and RB alterations define an alternative pathway driving neuroendocrine and small cell lung carcinomas. https://app.cochat.ai/papers/10.1002/ijc.29835
- The paper
- Meder, L., König, K., Ozretić, L., Schultheis, A. M., Ueckeroth, F., Ade, C. P., Albus, K., Boehm, D., Rommerscheidt‐Fuss, U., Florin, A., Buhl, T., Hartmann, W., Wolf, J., Merkelbach‐Bruse, S., Eilers, M., Perner, S., Heukamp, L. C., & Buettner, R. (2016). NOTCH, ASCL1, p53 and RB alterations define an alternative pathway driving neuroendocrine and small cell lung carcinomas. International Journal of Cancer. https://doi.org/10.1002/ijc.29835
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
