The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
BCL2A1 is a lineage-specific antiapoptotic melanoma oncogene that confers resistance to BRAF inhibition
Open accessAbstract
Although targeting oncogenic mutations in the BRAF serine/threonine kinase with small molecule inhibitors can lead to significant clinical responses in melanoma, it fails to eradicate tumors in nearly all patients. Successful therapy will be aided by identification of intrinsic mechanisms that protect tumor cells from death. Here, we used a bioinformatics approach to identify drug-able, “driver” oncogenes restricted to tumor versus normal tissues. Applying this method to 88 short-term melanoma cell cultures, we show that the antiapoptotic BCL2 family member BCL2A1 is recurrently amplified in ∼30% of melanomas and is necessary for melanoma growth. BCL2A1 overexpression also promotes melanomagenesis of BRAF-immortalized melanocytes. We find that high-level expression of BCL2A1 is restricted to melanoma due to direct transcriptional control by the melanoma oncogene MITF. Although BRAF inhibitors lead to cell cycle arrest and modest apoptosis, we find that apoptosis is significantly enhanced by suppression of BCL2A1 in melanomas with BCL2A1 or MITF amplification. Moreover, we find that BCL2A1 expression is associated with poorer clinical responses to BRAF pathway inhibitors in melanoma patients. Cotreatment of melanomas with BRAF inhibitors and obatoclax, an inhibitor of BCL2A1 and other BCL2 family members, overcomes intrinsic resistance to BRAF inhibitors in BCL2A1-amplified cells in vitro and in vivo. These studies identify MITF-BCL2A1 as a lineage-specific oncogenic pathway in melanoma and underscore its role for improved response to BRAF-directed therapy.
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
Improved survival with vemurafenib in melanoma with BRAF V600E mutation
Chapman, P. B., Hauschild, A., Robert, C., Haanen, J. B., Ascierto, P., Larkin, J., Dummer, R., Garbe, C., Testori, A., Maio, M., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1103782 · Cited by 7,720
The landscape of somatic copy-number alteration across human cancers
Beroukhim, R., Mermel, C. H., Porter, D., Wei, G., Raychaudhuri, S., Donovan, J., Barretina, J., Boehm, J. S., Dobson, J., Urashima, M., et al. (2010) · Nature · doi:10.1038/nature08822 · Cited by 4,017
Self-citationGarraway, L. A., Widlund, H. R., Rubin, M. A., Getz, G., Berger, A. J., Ramaswamy, S., Beroukhim, R., Milner, D. A., Granter, S. R., Du, J., et al. (2005) · Nature · doi:10.1038/nature03664 · Cited by 1,548
Self-citationCOT drives resistance to RAF inhibition through MAP kinase pathway reactivation
Johannessen, C. M., Boehm, J. S., Kim, S. Y., Thomas, S. R., Wardwell, L., Johnson, L. A., Emery, C. M., Stransky, N., Cogdill, A. P., Barretina, J., et al. (2010) · Nature · doi:10.1038/nature09627 · Cited by 1,460
Self-citationActivation of Apoptosis in Vivo by a Hydrocarbon-Stapled BH3 Helix
Walensky, L. D., Kung, A. L., Escher, I., Malia, T. J., Barbuto, S., Wright, R. D., Wagner, G., Verdine, G. L., & Korsmeyer, S. J. (2004) · Science · doi:10.1126/science.1099191 · Cited by 1,349
Characterizing the cancer genome in lung adenocarcinoma
Weir, B. A., Woo, M. S., Getz, G., Perner, S., Ding, L., Beroukhim, R., Lin, W. M., Province, M. A., Kraja, A., Johnson, L. A., et al. (2007) · Nature · doi:10.1038/nature06358 · Cited by 1,105
Self-citationCragg, M. S., Jansen, E. S., Cook, M., Harris, C., Strasser, A., & Scott, C. L. (2008) · Journal of Clinical Investigation · doi:10.1172/jci35437 · Cited by 207
Cited by
Toward Minimal Residual Disease-Directed Therapy in Melanoma
Rambow, F., Rogiers, A., Marin-Bejar, O., Aibar, S., Femel, J., Dewaele, M., Karras, P., Brown, D., Chang, Y. H., Debiec-Rychter, M., et al. (2018) · Cell · doi:10.1016/j.cell.2018.06.025 · Cited by 771
Self-citationLow MITF/AXL ratio predicts early resistance to multiple targeted drugs in melanoma
Müller, J., Krijgsman, O., Tsoi, J., Robert, L., Hugo, W., Song, C., Kong, X., Possik, P. A., Cornelissen-Steijger, P. D. M., Foppen, M. H. G., et al. (2014) · Nature Communications · doi:10.1038/ncomms6712 · Cited by 639
Targeting ER stress–induced autophagy overcomes BRAF inhibitor resistance in melanoma
Ma, X.-H., Piao, S.-F., Dey, S., Mcafee, Q., Karakousis, G., Villanueva, J., Hart, L. S., Levi, S., Hu, J., Zhang, G., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci70454 · Cited by 457
A melanocyte lineage program confers resistance to MAP kinase pathway inhibition
Johannessen, C. M., Johnson, L. A., Piccioni, F., Townes, A., Frederick, D. T., Donahue, M. K., Narayan, R., Flaherty, K. T., Wargo, J. A., Root, D. E., et al. (2013) · Nature · doi:10.1038/nature12688 · Cited by 452
Self-citationPhenotype plasticity as enabler of melanoma progression and therapy resistance
Arozarena, I., & Wellbrock, C. (2019) · Nature Reviews Cancer · doi:10.1038/s41568-019-0154-4 · Cited by 381
Metadata
- Authors
- Haq, R., Yokoyama, S., Hawryluk, E. B., Jönsson, G. B., Frederick, D. T., McHenry, K., Porter, D., Tran, T.-N., Love, K. T., Langer, R., Anderson, D. G., Garraway, L. A., Duncan, L. M., Morton, D. L., Hoon, D. S. B., Wargo, J. A., Song, J. S., & Fisher, D. E.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2013-02-27
- Volume
- 110
- Issue
- 11
- Pages
- 4321-4326
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2013178885
- Cited by
- 222
- References
- 7
- FWCI
- 11.70
- Type
- journal article
- Language
- en
- Open access
- bronze
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: BCL2A1 is a lineage-specific antiapoptotic melanoma oncogene that confers resistance to BRAF inhibition. https://app.cochat.ai/papers/10.1073/pnas.1205575110
- The paper
- Haq, R., Yokoyama, S., Hawryluk, E. B., Jönsson, G. B., Frederick, D. T., McHenry, K., Porter, D., Tran, T.-N., Love, K. T., Langer, R., Anderson, D. G., Garraway, L. A., Duncan, L. M., Morton, D. L., Hoon, D. S. B., Wargo, J. A., Song, J. S., & Fisher, D. E. (2013). BCL2A1 is a lineage-specific antiapoptotic melanoma oncogene that confers resistance to BRAF inhibition. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1205575110
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.
