The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
Activation of MET via Diverse Exon 14 Splicing Alterations Occurs in Multiple Tumor Types and Confers Clinical Sensitivity to MET Inhibitors
Published version of a preprint
Abstract
Focal amplification and activating point mutation of the MET gene are well-characterized oncogenic drivers that confer susceptibility to targeted MET inhibitors. Recurrent somatic splice site alterations at MET exon 14 (METex14) that result in exon skipping and MET activation have been characterized, but their full diversity and prevalence across tumor types are unknown. Here, we report analysis of tumor genomic profiles from 38,028 patients to identify 221 cases with METex14 mutations (0.6%), including 126 distinct sequence variants. METex14 mutations are detected most frequently in lung adenocarcinoma (3%), but also frequently in other lung neoplasms (2.3%), brain glioma (0.4%), and tumors of unknown primary origin (0.4%). Further in vitro studies demonstrate sensitivity to MET inhibitors in cells harboring METex14 alterations. We also report three new patient cases with METex14 alterations in lung or histiocytic sarcoma tumors that showed durable response to two different MET-targeted therapies. The diversity of METex14 mutations indicates that diagnostic testing via comprehensive genomic profiling is necessary for detection in a clinical setting. Significance: Here we report the identification of diverse exon 14 splice site alterations in MET that result in constitutive activity of this receptor and oncogenic transformation in vitro. Patients whose tumors harbored these alterations derived meaningful clinical benefit from MET inhibitors. Collectively, these data support the role of METex14 alterations as drivers of tumorigenesis, and identify a unique subset of patients likely to derive benefit from MET inhibitors. Cancer Discov; 5(8); 850–9. ©2015 AACR. See related commentary by Ma, p. 802. See related article by Paik et al., p. 842. This article is highlighted in the In This Issue feature, p. 783
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In the citing paper
“Importantly, large-scale profiling studies utilizing either whole exome sequencing or broad targeted sequencing panels in NSCLC tumors have revealed multiple non-random patterns of co-occurring or mutually exclusive mutations, which typically vary depending on the particular oncogenic driver mutation15, 34, 58–62.”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“Landmark large scale sequencing studies have established a census of major KRAS co-mutations in both early-stage and advanced LUAD15, 34, 59, 62.”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“Although EGFR –mutant tumors represent the prototypical oncogene-addicted LUAD subgroup that spearheaded adoption of the single-driver model, the overwhelming majority of EGFR-mutant lung tumors harbor one or more co-mutations, even when the analysis is limited to pre-defined sets of cancer-relevant genes within established panels (FoundationOne, Guardant360, MSK-IMPACT)15, 59, 72, 73.”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“NKX2–1 amplification is significantly enriched in EGFR-mutant LUAD”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“earlier studies that identified a central role for WNT signaling in LUAD metastasis”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“like CTNNB1 mutations, are encountered preferentially in advanced-stage tumors15, 34, 72, 73”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“but are less likely to harbor TP53 alterations (23.8%−26.5%) compared with other driver subgroups15, 128.”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“experimental data demonstrating increased invasive potential of EGFR and CTNNB1 co-mutated NSCLC cells in vitro15, 34, 72, 73, 120, 121”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“PIK3CA mutations, including classical kinase (H1074R and H1074L) and helical (E545K and E542K) domain mutations are observed in 9%−12.4% of advanced stage EGFR-mutant LUAD”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“Activating mutations in CTNNB1 represent one of the most consistently co-selected alterations in EGFR-mutant LUAD across different studies.”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“advanced-stage ALK-rearrangement -positive LUAD are enriched in somatic alterations in CDKN2A (32.5%)”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“and CDKN2B (26.5%)”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“their prevalence increases in late-stage tumors (5.3% - 9.6%)”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“these tumors are characterized by highly significant enrichment of MDM2 and CDK4 amplification (41.6%) compared with other driver oncogenes”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“both RET and ROS1 fusion-positive LUAD are characterized by high rates of concurrent CDKN2A loss (29.8% and 30.4% for RET and ROS1-rearranged tumors respectively)”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“CDKN2B loss (25% and 17.7% respectively)”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“The spectrum of co-occurring alterations in BRAF-mutant NSCLC mirrors the background frequency of alterations in TP53 (53.3%), LKB1 (16.2%), ATM (5.8%), NF1 (6.9%), PIK3CA (6.6%), KEAP1 (6.6%), MYC (10.8%), NKX2–1 (7.3%)”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“as well as frequent mutations in RB1 (8.9%)”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“whereas loss of CDKN2A (24.1%) and CDKN2B (17.5%) occur with similar frequencies to that in the overall population of patients with NSCLC15.”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“both RET and ROS1 fusion-positive LUAD are characterized by high rates of concurrent CDKN2A loss (29.8% and 30.4% for RET and ROS1-rearranged tumors respectively)”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“although the frequency of TP53 mutations appears to be somewhat higher compared to ALK-rearranged tumors (34.6%−45.5% for RET-and 45.6% for ROS1- rearranged tumors)15, 131.”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“patients with ERBB2-mutant NSCLC exhibit preferential amplification of NKX2–1 (19.4%) and ERBB2 itself (14.4%)”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“as well as amplification of MET itself15.”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“CDKN2B loss (25% and 17.7% respectively)”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“relative paucity of TP53 mutations”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“but the frequencies of co-mutations in TP53 (51.7%), CDKN2A (27.2%), CDKN2B (17.2%), PIK3CA (5%), CTNNB1 (4.4%) and MDM2 amplification (7.2%) are similar to that observed in the overall population of patients with NSCLC15.”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“In contrast, mutations in TP53 (33.57%) are under-represented”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“although alterations in RB1, MDM2, CDKN2A (16.6%) and CDKN2B (11.2%) are less frequent within this molecular subgroup15.”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
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“Hybrid capture-based NGS panels have produced fewer false-negative results compared to whole-exome panels.(17,20,21) RNA-based PCR assays detect a fusion transcript between MET exon 13 and 15.”
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“Besides NSCLC,METex14 skipping has only rarely been noted in other solid tumors, including brain glioma (12), although a higher prevalence has been reported in secondary glioblastoma (13).”
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“Mutations of the splice site of MET exon 14 are quite rare, found in 3% to 4% of NSCLC [19].”
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“18,25 Nevertheless, likely as a result of low allele frequency, MET exon14 mutations can occasionally co-occur with mutations in KRAS , ROS1 , and EGFR driver mutations, 18,34 essentially signifying pre-existing resistance to MET TKI monotherapy.”
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written on behalf of the AME Lung Cancer Collaborative Group, Feng, Y., Feng, G., Lu, X., Qian, W., Ye, J., Manrique, C. A., Ma, C., & Lu, Y. (2018) · Journal of Thoracic Disease · doi:10.21037/jtd.2018.09.108 · Cited by 20
Self-citationPatient removals from general practitioner lists in Northern Ireland: 1987-1996.
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The genomic landscape of lung cancer in never-smokers from the Women’s Health Initiative
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“We observed MET exon 14 skipping mutations at a higher prevalence than previous studies (5, 38), with a trend toward exclusivity to the never-/light smoker group (8 of 56 [14”
Inhibition of KIT Tyrosine Kinase Activity: Two Decades After the First Approval
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The Current Landscape for METex14 Skipping Mutations in Non–Small Cell Lung Cancer
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“The mesenchymal-epithelial transition (MET) oncogene encodes for the hepatocyte growth receptor, which is a tyrosine kinase (Frampton et al., 2015).”
BackgroundClinical Relevance of Targeted Therapy and Immune-Checkpoint Inhibition in Lung Cancer
Leone, G. M., Candido, S., Lavoro, A., Vivarelli, S., Gattuso, G., Călina, D. C., Libra, M., & Falzone, L. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15041252 · Cited by 21
Targeting MET Amplification: Opportunities and Obstacles in Therapeutic Approaches
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“One such alteration is exon 14 skipping, which results in an aberrant MET protein lacking a critical regulatory domain [10].”
BackgroundApplication of CRISPR-mediated genome engineering in cancer research
Sayin, V. I., & Papagiannakopoulos, T. Y. (2016) · Cancer Letters · doi:10.1016/j.canlet.2016.03.029 · Cited by 20
McCoach, C. E., Bivona, T. G., Blakely, C. M., & Doebele, R. C. (2016) · Clinical Lung Cancer · doi:10.1016/j.cllc.2016.05.025 · Cited by 19
Sequencing Therapy for Genetically Defined Subgroups of Non–Small Cell Lung Cancer
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Analysis of MET kinase domain rearrangement in NSCLC
Zhuo, M., Liang, Z., Yi, Y., Wu, N., Yang, X., Zhong, J., Chen, X., Huang, Y. X., Yu, Z., Liu, C., et al. (2020) · Lung Cancer · doi:10.1016/j.lungcan.2020.04.040 · Cited by 19
Real-world insights into patients with advanced NSCLC and MET alterations
Bittoni, M. A., Yang, J. C., Shih, J., Peled, N., Smit, E. F., Camidge, D. R., Arasada, R. R., Oksen, D., Boutmy, E., Stroh, C., et al. (2021) · Lung Cancer · doi:10.1016/j.lungcan.2021.06.015 · Cited by 20
Kumaki, Y., Olsen, S., Suenaga, M., Nakagawa, T., Uetake, H., & Ikeda, S. (2021) · Current Oncology · doi:10.3390/curroncol28050317 · Cited by 18
“MET exon 14 skipping has been described as a driver mutation in non-small cell lung cancer (NSCLC) [3], and approximately 3% of NSCLC patients are reported to have MET exon 14 skipping [4].”
BackgroundWang, F., Daylan, A. E. C., Deng, L., Yang, J., Sharma, J. N., Su, C. T., Li, S., Zang, X., Halmos, B., Borczuk, A., et al. (2023) · Cancers · doi:10.3390/cancers15133372 · Cited by 18
Krebs, M., Cho, B. C., Hiret, S., Han, J., Lee, K. H., Pérez, C. L., de Braud, F., Haura, E. B., Sanborn, R. E., Yang, J. C., et al. (2025) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2025.05.012 · Cited by 18
Self-citationZhang, J., Lu, S., Yu, Y., & Zhang, Q. (2019) · Journal of Cancer Research and Therapeutics · doi:10.4103/jcrt.jcrt_591_18 · Cited by 18
Zhou, C., Tian, J., Lin, P., Liu, T., He, A., Fang, L., & Sun, L. (2020) · Bioanalysis · doi:10.4155/bio-2020-0011 · Cited by 18
Targeting the MET-Signaling Pathway in Non-Small–Cell Lung Cancer: Evidence to Date
Bylicki, O., Paleiron, N., Assié, J., & CHOUAID, C. (2020) · OncoTargets and Therapy · doi:10.2147/ott.s219959 · Cited by 19
Reuss, J. E., Gosa, L., & Liu, S. V. (2021) · Clinical Lung Cancer · doi:10.1016/j.cllc.2021.07.011 · Cited by 18
Jiang, Z., Gu, Z., Yu, X.-M., Cheng, T., & Liu, B. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1447678 · Cited by 22
Targeting the MET Pathway in Gastric and Oesophageal Cancers: Refining the Optimal Approach
Lee, J., Tran, P. N., & Klempner, S. J. (2016) · Clinical Oncology · doi:10.1016/j.clon.2016.01.009 · Cited by 17
Targeting microtubule sensitizes drug resistant lung cancer cells to lysosomal pathway inhibitors
Chin, T., Gandhi, T. K. B., Man, E. P. S., Clohessy, J. G., Csizmadia, E., Quinlan, M. P., Putti, T. C., Wan, S., Xie, C., Ali, A., et al. (2020) · Theranostics · doi:10.7150/thno.38729 · Cited by 17
“Recent studies have also reported mutations in c-kit, MET, and PDGF receptors resulting in abnormal trafficking [50-53].”
BackgroundFogli, S., Tabbò, F., Capuano, A., Re, M. D., Passiglia, F., Cucchiara, F., Scavone, C., Gori, V., Novello, S., Schmidinger, M., et al. (2022) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2022.103602 · Cited by 17
Refining patient selection of MET-activated non-small cell lung cancer through biomarker precision
Lai, G. G. Y., Guo, R., Drilon, A. E. D. C., & Tan, D. S. W. (2022) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2022.102444 · Cited by 17
Fernandes, M., Paget, S., Kherrouche, Z., Truong, M., Vinchent, A., Meneboo, J., Sebda, S., Werkmeister, E., Descarpentries, C., Figeac, M., et al. (2023) · FEBS Letters · doi:10.1002/1873-3468.14702 · Cited by 21
Genetic screening and molecular characterization of MET alterations in non-small cell lung cancer
Saigí, M., Leer, A. M., Pros, E., Nadal, E., Brambilla, E. M., & Sánchez‐Céspedes, M. (2017) · Clinical & Translational Oncology · doi:10.1007/s12094-017-1799-7 · Cited by 17
“In all these cases, the tumor is highly dependent on MET activity and the tumor is, therefore, potentially sensitive to treatment with TKIs targeting MET (MET-TKIs) [9, 10].”
BackgroundEffective implementation of novel MET pharmacodynamic assays in translational studies
Srivastava, A. K., Navas, T. A., Herrick, W. G., Hollingshead, M. G., Bottaro, D. P., Doroshow, J. H., & Parchment, R. E. (2017) · Annals of Translational Medicine · doi:10.21037/atm.2016.12.78 · Cited by 16
Safety of Tepotinib in Patients With MET Exon 14 Skipping NSCLC and Recommendations for Management
Veillon, R., Sakai, H., Le, X., Felip, E., Cortot, A. B., Smit, E. F., Park, K., Griesinger, F., Britschgi, C., Wu, Y.-L. L. C., et al. (2022) · Clinical Lung Cancer · doi:10.1016/j.cllc.2022.03.002 · Cited by 16
Fregni, M., Ciribilli, Y., & Zawacka‐Pankau, J. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23137213 · Cited by 16
“and from samples referred to the Foundation Medicine [18].”
BackgroundXu, L., Wang, F., & Luo, F. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.1013299 · Cited by 16
Potent antitumor activity of ensartinib in MET exon 14 skipping-mutated non-small cell lung cancer
Xia, Y., Jin, R., Li, M., Lan, F., Zhu, H., Yu, Y., Miao, D., Wang, Q., Zhou, Y., Selvaggi, G., et al. (2023) · Cancer Letters · doi:10.1016/j.canlet.2023.216140 · Cited by 16
The development of amivantamab for the treatment of non-small cell lung cancer
Brazel, D., & Nagasaka, M. (2023) · Respiratory Research · doi:10.1186/s12931-023-02558-4 · Cited by 19
“MET is overexpressed in 20%, [20] amplified in 1–5%, [21] and exon 14 skipping mutations ( MET ex14) occur in 3–4% of NSCLC tumors [22–24].”
BackgroundUnderstanding variants of unknown significance and classification of genomic alterations
Pavlick, D. C., Frampton, G. M., & Ross, J. R. (2024) · The Oncologist · doi:10.1093/oncolo/oyae149 · Cited by 16
“25 In glioma, EGFR splice variants including deletion of EGFR exons 2-7 (EGFRvIII) result in ligand-independent constitutive signaling to downstream pathways.”
BackgroundSelf-citationSmith, M. A., Licata, T., Lakhani, A., Garcia, M. V., Schildhaus, H., Vuaroqueaux, V., Halmos, B., Borczuk, A., Chen, Y. A., Creelan, B., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-3006 · Cited by 17
Blidner, R., Haynes, B. C., Hyter, S. D., Schmitt, S., Pessetto, Z. Y., Godwin, A. K., Su, D., Hurban, P., van Kempen, L. C. L. T., Aguirre, M. L., et al. (2018) · Journal of Molecular Diagnostics · doi:10.1016/j.jmoldx.2018.10.003 · Cited by 14
Ahn, M., Mendoza, M. J., Pavlakis, N., Kato, T., Soo, R. A., Kim, D., Liam, C. K., Hsia, T., Lee, C. K., Reungwetwattana, T., et al. (2022) · Clinical Lung Cancer · doi:10.1016/j.cllc.2022.07.012 · Cited by 16
Self-citationEstevam, G. O., Linossi, E., Rao, J., Macdonald, C. B., Ravikumar, A., Chrispens, K. M., Capra, J. A., Coyote-Maestas, W., Pimentel, H., Collisson, E. A., et al. (2025) · eLife · doi:10.7554/elife.101882 · Cited by 17
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“MET aberrations have been extensively analyzed in various oncogenic processes and have been proven as a powerful facilitator in the invasion of tumor, angiogenesis, and metastasis [91].”
Lung cancer as a paradigm for precision oncology in solid tumours
Schallenberg, S., Merkelbach‐Bruse, S., & Buettner, R. (2017) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s00428-017-2183-2 · Cited by 17
Carlo, E. D., Bertoli, E., Conte, A. D., Stanzione, B., Berto, E., Revelant, A., Spina, M., & Bearz, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23126477 · Cited by 15
“METexon14 skipping mutations (METex14) represent 3–4% of NSCLC [80].”
BackgroundOncogenic KRAS alters splicing factor phosphorylation and alternative splicing in lung cancer
Lo, A., McSharry, M. V., & Berger, A. H. (2022) · BMC Cancer · doi:10.1186/s12885-022-10311-1 · Cited by 16
RNA splicing alterations in lung cancer pathogenesis and therapy
Yan, Y., Ren, Y., Bao, Y., & Wang, Y. (2023) · Cancer Pathogenesis and Therapy · doi:10.1016/j.cpt.2023.04.004 · Cited by 16
Estevam, G. O., Linossi, E. M., Macdonald, C. B., Espinoza, C. A., Michaud, J. M., Coyote-Maestas, W., Collisson, E. A., Jura, N., & Fraser, J. S. (2024) · eLife · doi:10.7554/elife.91619 · Cited by 22
“The METΔEx14 variant maintains the ligand-binding ECD and is oncogenic in part due to a combination of increased ligand sensitivity and reduced degradation due to the loss of a Cbl ubiquitin ligase interaction (Frampton et al., 2015; Abella et al., 2005; Pechard et al., 2001; Kong-beltran et al., 2006).”
Self-citationSomatic mutations and immune checkpoint biomarkers
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Subramanian, J., & Tawfik, O. W. (2021) · Expert Review of Anticancer Therapy · doi:10.1080/14737140.2021.1924683 · Cited by 15
“Both RNA-based and DNA-based approaches have been used to detect METex14 in NSCLC [1,27,39,45,46,56].”
BackgroundMethodInfluentialDempke, W. C. M., & Fenchel, K. (2021) · Translational Lung Cancer Research · doi:10.21037/tlcr-21-124 · Cited by 15
“This leads to c-MET ubiquitination abrogation, increased c-MET protein stability, and impaired c-MET degradation which then, in turn, induces ligand-independent c-MET activation (13,14).”
BackgroundDamalanka, V. C., Voss, J. J. L. P., Mahoney, M. W., Primeau, T. M., Li, S., Klampfer, L., & Janetka, J. W. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c01671 · Cited by 15
Liquid Biopsy Analysis as a Tool for TKI-Based Treatment in Non-Small Cell Lung Cancer
Buszka, K., Ntzifa, A., Owecka, B., Kamińska, P., Kolecka-Bednarczyk, A., Zabel, M., Nowicki, M. O., Lianidou, E. S., & Budna, J. (2022) · Cells · doi:10.3390/cells11182871 · Cited by 15
Henzler, C. M., Schomaker, M. L., Yang, R., Lambert, A. P., LaRue, R. S., Kincaid, R., Beckman, K. B., Kemmer, T., Wilson, J. D., Yohe, S. L., et al. (2018) · Annals of Translational Medicine · doi:10.21037/atm.2018.05.07 · Cited by 15
“A 93-base pair FLT3 ITD was missed in a BM specimen due to a subthreshold ( 1”
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Sun, S., Du, W., Sun, Q., Zhao, X. Q., Qin, B., Shi, D., Wan, C., & Wu, Z. (2021) · Cancer Medicine · doi:10.1002/cam4.4178 · Cited by 13
MET (c-Met) protein overexpression is an emerging protein biomarker in non-small cell lung cancer
Tsao, M., Sholl, L. M., Shiller, M., Illei, P. B., Wistuba, I. I., Beasley, M. B., Schalper, K. A., Simmons, A. R., Ansell, P. J., Beruti, S., et al. (2025) · npj Precision Oncology · doi:10.1038/s41698-025-01144-9 · Cited by 14
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REIA: A database for cancer A-to-I RNA editing with interactive analysis
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“Alternative splicing, a key factor in prognostic analysis, also affects the individual changes in regulatory binding sites and the alterations to protein-coding sequences [57-60], but its association with the RNA editing is not yet explored.”
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“Indeed, gene amplification, activating mutations, and specific lesions such asMET exon 14 skipping, as well as RNA overexpression, have all been shown to render malignant cells dependent on MET signaling to sustain growth, proliferation, and other oncogenic features (46).”
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Special issue: “MET as actionable target in cancer therapy”
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“Most interestingly, it has also been subsequently confirmed to be present in a multitude of other diverse human cancer types, primarily as a result of wide adoption of clinical cancer genomic profiling analysis (19,20) .”
Metadata
- Authors
- Frampton, G. M., Ali, S. M., Rosenzweig, M., Chmielecki, J., Lu, X., Bauer, T. M., Akimov, M., Bufill, J. A., Lee, C., Jentz, D., Hoover, R., Ou, S.-H. I., Salgia, R., Brennan, T., Chalmers, Z. R., Jaeger, S., Huang, A., Elvin, J. A., Erlich, R., Fichtenholtz, A., Gowen, K. A., Greenbowe, J., Johnson, A., Khaira, D., McMahon, C., Sanford, E. M., Roels, S., White, J., Greshock, J., Schlegel, R., Lipson, D., Yelensky, R., Morosini, D., Ross, J. S., Collisson, E., Peters, M., Stephens, P. J., & Miller, V. A.
- Affiliations
- Foundation Medicine (United States) (US)
- University of California, San Francisco (US)
- Tennessee Oncology (US)
- Novartis (Switzerland) (CH)
- 5Michiana Hematology-Oncology, PC, Mishawaka, Indiana.
- University of North Carolina at Chapel Hill (US)
- South Bend Medical Foundation (US)
- University of California, Irvine (US)
- University of Chicago (US)
- 1Foundation Medicine Inc., Cambridge, Massachusetts.
- Corresponding author
- Frampton, Garrett M.
- ORCID
- Frampton, Garrett M.
- Ali, Siraj M.
- Rosenzweig, Mark
- Chmielecki, Juliann
- Lu, Xinyuan
- Bauer, Todd M.
- Akimov, Mikhail
- Lee, Carrie
- Ou, Sai-Hong Ignatius
- Salgia, Ravi
- Chalmers, Zachary R.
- Huang, Alan
- Elvin, Julia A.
- Johnson, Adrienne
- Sanford, Eric M.
- Roels, Steven
- Greshock, Joel
- Lipson, Doron
- Yelensky, Roman
- Ross, Jeffrey S.
- Collisson, Eric
- Miller, Vincent A.
- Venue
- Cancer Discovery
- Published
- 2015-08-01
- Volume
- 5
- Issue
- 8
- Pages
- 850-859
- ISSN
- 2159-8274 (ISSN-L)
- 2159-8290
- OpenAlex
- W2160212814
- Cited by
- 796
- References
- 41
- Citations by year
- 2026: 26 · 2025: 47 · 2024: 69 · 2023: 83 · 2022: 73 · 2021: 97 · 2020: 91 · 2019: 71 · 2018: 71 · 2017: 86 · 2016: 65 · 2015: 13
- FWCI
- 62.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Discovery (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (P30CA016086)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Mechanisms and Therapy
- Keywords
- MET activation, MET inhibitors, exon skipping, lung adenocarcinoma, glioma, histiocytic sarcoma, targeted therapy sensitivity, oncogenic transformation, comprehensive genomic profiling, tumor genomic profiles
- MeSH terms
- Aged, Aged, 80 and over, Antineoplastic Agents, Exons, Female, Humans, Immunohistochemistry, Male, Mutation, Neoplasm Staging, Neoplasms, Tomography, X-Ray Computed, Cluster Analysis, Alternative Splicing, Drug Resistance, Neoplasm, Proto-Oncogene Proteins c-met, Gene Expression Profiling, Genomics, Protein Kinase Inhibitors
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