K‐RasV14I‐induced Noonan syndrome predisposes to tumour development in mice
Abstract
The Noonan syndrome (NS) is an autosomal dominant genetic disorder characterized by short stature, craniofacial dysmorphism, and congenital heart defects. A significant proportion of NS patients may also develop myeloproliferative disorders (MPDs), including juvenile myelomonocytic leukaemia (JMML). Surprisingly, scarce information is available in relation to other tumour types in these patients. We have previously developed and characterized a knock-in mouse model that carries one of the most frequent KRAS-NS-related mutations, the K-Ras(V14I) substitution, which recapitulates most of the alterations described in NS patients, including MPDs. The K-Ras(V14I) mutation is a mild activating K-Ras protein; thus, we have used this model to study tumour susceptibility in comparison with mice expressing the classical K-Ras(G12V) oncogene. Interestingly, our studies have shown that these mice display a generalized tumour predisposition and not just MPDs. In fact, we have observed that the K-Ras(V14I) mutation is capable of cooperating with the p16Ink4a/p19Arf and Trp53 tumour suppressors, as well as with other risk factors such as pancreatitis, thereby leading to a higher cancer incidence. In conclusion, our results illustrate that the K-Ras(V14I) activating protein is able to induce cancer, although at a much lower level than the classical K-Ras(G12V) oncogene, and that it can be significantly modulated by both genetic and non-genetic events. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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V14 is an important hub in the KRAS hydrophobic interaction network.
“Supporting the fact that V14 is an important hub in the KRAS hydrophobic interaction network”
Cites
Siegel, R., Naishadham, D., & Jemal, A. (2013) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21166 · Cited by 11,825 · see citing works
Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours
Donehower, L. A., Harvey, M., Slagle, B. L., McArthur, M. J., Montgomery, C. A., Butel, J. S., & Bradley, A. (1992) · Nature · doi:10.1038/356215a0 · Cited by 4,649 · see citing works
Hingorani, S. R., Wang, L., Multani, A. S., Combs, C., Deramaudt, T. B., Hruban, R. H., Rustgi, A. K., Chang, S., & Tuveson, D. A. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.04.023 · Cited by 2,609 · see citing works
Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse
Hingorani, S. R., Petricoin, E. F., Maitra, A., Rajapakse, V., King, C., Jacobetz, M. A., Ross, S., Conrads, T. P., Veenstra, T. D., Hitt, B. A., et al. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00309-x · Cited by 2,471 · see citing works
COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer
Forbes, S. A., Bindal, N., Bamford, S., Cole, C., Kok, C. Y., Beare, D., Jia, M., Shepherd, R., Leung, K., Menzies, A., et al. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkq929 · Cited by 2,278 · see citing works
Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes
Almoguera, C., Shibata, D. K., Forrester, K., Wj, M., Arnheim, N., & Perucho, M. (1988) · Cell · doi:10.1016/0092-8674(88)90571-5 · Cited by 2,100 · see citing works
Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-rasPreprint
Jackson, E. L., Willis, N. A., Mercer, K. L., Bronson, R. T., Crowley, D. G., Montoya, R., Jacks, T., & Tuveson, D. A. (2001) · Genes & Development · doi:10.1101/gad.943001 · Cited by 1,877 · see citing works
Role of the INK4a Locus in Tumor Suppression and Cell Mortality
Serrano, M., Lee, H.-W., Chin, L., Cordon-Cardo, C., Beach, D., & DePinho, R. A. (1996) · Cell · doi:10.1016/s0092-8674(00)81079-x · Cited by 1,585 · see citing works
Hyperactive Ras in developmental disorders and cancer
Schubbert, S., Shannon, K., & Bollag, G. (2007) · Nature Reviews Cancer · doi:10.1038/nrc2109 · Cited by 1,583 · see citing works
Genetics and biology of pancreatic ductal adenocarcinomaPreprint
Hezel, A. F., Kimmelman, A. C., Stanger, B. Z., Bardeesy, N. M., & DePinho, R. A. (2006) · Genes & Development · doi:10.1101/gad.1415606 · Cited by 1,570 · see citing works
Guerra, C., Schuhmacher, A. J., Cañamero, M., Grippo, P. J., Verdaguer, L., Pérez-Gallego, L., Dubus, P., Sandgren, E. P., & Barbacid, M. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.01.012 · Cited by 1,224 · see citing works
Self-citationSomatic activation of the K-ras oncogene causes early onset lung cancer in mice
Johnson, L., Mercer, K., Greenbaum, D., Bronson, R. T., Crowley, D., Tuveson, D. A., & Jacks, T. (2001) · Nature · doi:10.1038/35074129 · Cited by 1,179 · see citing works
LKB1 modulates lung cancer differentiation and metastasis
Ji, H., Ramsey, M. R., Hayes, D. N., Fan, C., McNamara, K., Kozlowski, P., Torrice, C., Wu, M. C., Shimamura, T., Perera, S. A., et al. (2007) · Nature · doi:10.1038/nature06030 · Cited by 1,064 · see citing works
Aguirre, A. J., Bardeesy, N., Sinha, M., Lopez, L., Tuveson, D. A., Horner, J., Redston, M. S., & DePinho, R. A. (2003) · Genes & Development · doi:10.1101/gad.1158703 · Cited by 1,033 · cited 2× · see citing works
“Although K-Ras oncogenes and p16Ink4a/p19Arf loss cooperate, accelerating PDAC and lung tumour development in mouse models [34,45,46], no other tumours were found in K-RasV14I;p16Ink4a/p19Arf −/− mice.”
BackgroundRas in Cancer and Developmental Diseases
Fernández‐Medarde, A., & Santos, E. (2011) · Genes & Cancer · doi:10.1177/1947601911411084 · Cited by 959 · see citing works
Rauen, K. A. (2013) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-091212-153523 · Cited by 877 · see citing works
Tuveson, D. A., Shaw, A. T., Willis, N. A., Silver, D. P., Jackson, E. L., Chang, S., Mercer, K. L., Grochow, R., Hock, H., Crowley, D., et al. (2004) · Cancer Cell · doi:10.1016/s1535-6108(04)00085-6 · Cited by 798 · see citing works
Roberts, A. E., Allanson, J. E., Tartaglia, M., & Gelb, B. D. (2013) · The Lancet · doi:10.1016/s0140-6736(12)61023-x · Cited by 791 · see citing works
Germline KRAS mutations cause Noonan syndrome
Schubbert, S., Zenker, M., Rowe, S. L., Böll, S., Klein, C., Bollag, G., van der Burgt, I., Musante, L., Kalscheuer, V., Wehner, L.-E., et al. (2006) · Nature Genetics · doi:10.1038/ng1748 · Cited by 730 · see citing works
Maitra, A., & Hruban, R. H. (2008) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev.pathmechdis.3.121806.154305 · Cited by 707 · see citing works
Tumor induction by an endogenous K-ras oncogene is highly dependent on cellular context
Guerra, C. E., Mijimolle, N., Dhawahir, A., Dubus, P. R., Barradas, M., Serrano, M., Campuzano, V., & Barbacid, M. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00191-0 · Cited by 566 · see citing works
Self-citationThe Differential Effects of Mutant <i>p53</i> Alleles on Advanced Murine Lung Cancer
Jackson, E. L., Olive, K. P., Tuveson, D. A., Bronson, R., Crowley, D., Brown, M., & Jacks, T. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-2193 · Cited by 553 · see citing works
Guerra, C., Collado, M., Navas, C., Schuhmacher, A. J., Hernández-Porras, I., Cañamero, M., Rodriguez-Justo, M., Serrano, M., & Barbacid, M. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.05.011 · Cited by 516 · see citing works
Self-citationRisk of pancreatic adenocarcinoma in chronic pancreatitis
Malka, D., Hammel, P. R., Maire, F., Rufat, P., Madeira, I., Pessione, F., Lévy, P., & Ruszniewski, P. B. (2002) · Gut · doi:10.1136/gut.51.6.849 · Cited by 456 · see citing works
Noonan syndrome and clinically related disorders
Tartaglia, M., Gelb, B. D., & Zenker, M. (2011) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2010.09.002 · Cited by 420 · see citing works
Puyol, M., Martín, A., Dubus, P., Mulero, F., Pizcueta, P., Khan, G., Guerra, C., Santamaría, D., & Barbacid, M. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.05.025 · Cited by 415 · see citing works
Self-citationGain-of-Function Mutations in RIT1 Cause Noonan Syndrome, a RAS/MAPK Pathway Syndrome
Aoki, Y., Niihori, T., Banjo, T., Okamoto, N., Mizuno, S., Kurosawa, K., Ogata, T., Takada, F., Yano, M., Ando, T., et al. (2013) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2013.05.021 · Cited by 331 · see citing works
Wildtype Kras2 can inhibit lung carcinogenesis in mice
Zhang, Z., Wang, Y., Vikis, H. G., Johnson, L., Liu, G., Li, J., Anderson, M. W., Sills, R. C., Hong, H. L. T., Devereux, T. R., et al. (2001) · Nature Genetics · doi:10.1038/ng721 · Cited by 295 · see citing works
Cancer in Noonan, Costello, cardiofaciocutaneous and LEOPARD syndromes
Kratz, C. P., Rapisuwon, S., Reed, H., Hasle, H., & Rosenberg, P. S. (2011) · American Journal of Medical Genetics Part C Seminars in Medical Genetics · doi:10.1002/ajmg.c.30300 · Cited by 221 · see citing works
Kratz, C. P., Franke, L., Peters, H., Kohlschmidt, N., Kazmierczak, B., Finckh, U., Bier, A., Eichhorn, B., Blank, C. U., Kraus, C. S., et al. (2015) · British Journal of Cancer · doi:10.1038/bjc.2015.75 · Cited by 217 · see citing works
Tumor predisposition in Costello syndrome
Gripp, K. W. (2005) · American Journal of Medical Genetics Part C Seminars in Medical Genetics · doi:10.1002/ajmg.c.30065 · Cited by 193 · see citing works
Estep, A. L., Tidyman, W. E., Teitell, M. A., Cotter, P. D., & Rauen, K. A. (2005) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.31078 · Cited by 180 · see citing works
Genetically engineered mouse models of pancreatic adenocarcinoma
Guerra, C. E., & Barbacid, M. (2013) · Molecular Oncology · doi:10.1016/j.molonc.2013.02.002 · Cited by 179 · see citing works
Self-citationCancer risk in patients with Noonan syndrome carrying a PTPN11 mutation
Jongmans, M. C. J., van der Burgt, I., Hoogerbrugge, P. M., Noordam, C., Yntema, H. G., Nillesen, W. M., Kuiper, R. P., Ligtenberg, M. J. L., van Kessel, A. G., van Krieken, J. H., et al. (2011) · European Journal of Human Genetics · doi:10.1038/ejhg.2011.37 · Cited by 178 · see citing works
Identification of cancer initiating cells in K-Ras driven lung adenocarcinoma
Mainardi, S., Mijimolle, N., Francoz, S., Vicente‐Dueñas, C., Sánchez-Garcı́a, I., & Barbacid, M. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1320383110 · Cited by 165 · see citing works
Gremer, L., Merbitz-Zahradnik, T., Dvorsky, R., Cirstea, I. C., Kratz, C. P., Zenker, M., Wittinghofer, A., & Ahmadian, M. R. (2011) · Human Mutation · doi:10.1002/humu.21377 · Cited by 158 · see citing works
Hematopoiesis and leukemogenesis in mice expressing oncogenic NrasG12D from the endogenous locus
Li, Q., Haigis, K. M., McDaniel, A., Harding-Theobald, E. R., Kogan, S. C., Akagi, K., Wong, J. C. Y., Braun, B. S., Wolff, L., Jacks, T., et al. (2010) · Blood · doi:10.1182/blood-2010-04-280750 · Cited by 154 · see citing works
Kwon, M.-C., & Berns, A. J. M. (2013) · Molecular Oncology · doi:10.1016/j.molonc.2013.02.010 · Cited by 145 · see citing works
Flex, E., Jaiswal, M., Pantaleoni, F., Martinelli, S., Strullu, M., Fansa, E. K., Caye‐Eude, A., Luca, A. D., Lepri, F. R., Dvorský, R., et al. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu148 · Cited by 145 · see citing works
Grabocka, E., Pylayeva‐Gupta, Y., Jones, M. V., Lubkov, V., Yemanaberhan, E., Taylor, L. J., Jeng, H. H., & Bar‐Sagi, D. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.01.005 · Cited by 141 · see citing works
Niemeyer, C. M. (2014) · Haematologica · doi:10.3324/haematol.2014.114595 · Cited by 140 · see citing works
Chen, X., Mitsutake, N., LaPerle, K., Akeno, N., ZANZONICO, P. B., Longo, V. A., Mitsutake, S., Kimura, E. T., Geiger, H., Santos, E., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0900343106 · Cited by 139 · see citing works
A mouse model for Costello syndrome reveals an Ang II–mediated hypertensive condition
Schuhmacher, A. J., Guerra, C. E., Sauzeau, V., Cañamero, M., Bustelo, X. R., & Barbacid, M. (2008) · Journal of Clinical Investigation · doi:10.1172/jci34385 · Cited by 112 · see citing works
Self-citationAutoimmune disease and multiple autoantibodies in 42 patients with RASopathies
Quaio, C. R. D. C., de Carvalho, J. F., Silva, C. A., Bueno, C., Brasil, A. S., Pereira, A. C., Jorge, A. A. L., Malaquias, A. C., Kim, C. A., & Bertola, D. R. (2012) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.35290 · Cited by 99 · see citing works
Biochemical and Functional Characterization of Germ Line KRAS Mutations
Schubbert, S., Bollag, G. E., Lyubynska, N., Nguyen, H. T., Kratz, C. P., Zenker, M., Niemeyer, C. M., Molven, A., & Shannon, K. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.00965-07 · Cited by 99 · see citing works
K-Ras <sup>V14I</sup> recapitulates Noonan syndrome in mice
Hernández-Porras, I., Fabbiano, S., Schuhmacher, A. J., Aicher, A., Cañamero, M., Cámara, J. A., Cussó, L., Desco, M., Heeschen, C., Mulero, F., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1418126111 · Cited by 96 · see citing works
Self-citationSimpson, A. J., Wallace, W. A., Marsden, M. E., Govan, J. R. W., Porteous, D. J., Haslett, C., & Sallenave, J. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.3.1778 · Cited by 89 · see citing works
LOH of chromosome 12p correlates with Kras2 mutation in non-small cell lung cancer
Li, J., Zhang, Z., Zunyan Dai, Y., Plass, C., Morris, Q., Wang, Y., Wiest, J. S., Anderson, M. W., & You, M. (2003) · Oncogene · doi:10.1038/sj.onc.1206192 · Cited by 58 · see citing works
Díaz, R., Ahn, D. H., Lopez-Barcons, L. A., Malumbres, M., de Castro, I. P., Lue, J., Ferrer‐Miralles, N., Mangues, R., Tsong, J., Garcia, R., et al. (2002) · PubMed · Cited by 50 · see citing works
Malignancy in Noonan syndrome and related disorders
Smpokou, P., Zand, D. J., Rosenbaum, K. N., & Summar, M. L. (2015) · Clinical Genetics · doi:10.1111/cge.12568 · Cited by 46 · see citing works
Lo, F., Lin, J., Kuo, M.-T., Chiu, P., Shu, S., Chao, M., Lee, Y., & Lin, S. (2008) · European Journal of Pediatrics · doi:10.1007/s00431-008-0858-z · Cited by 36 · see citing works
Noonan syndrome and systemic lupus erythematosus in a patient with a novel KRAS mutation.
Leventopoulos, G., Denayer, E., Makrythanasis, P., Papapolychroniou, C., & Fryssira, H. (2010) · PubMed · Cited by 29 · see citing works
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Chen, J., Zhang, S., Wang, W., Pang, L., Zhang, Q., & Liu, X. (2021) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.0c01470 · Cited by 140 · see citing works
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Pantsar, T., Rissanen, S., Dauch, D., Laitinen, T., Vattulainen, I., & Poso, A. (2018) · PLOS Computational Biology · doi:10.1371/journal.pcbi.1006458 · Cited by 85 · see citing works
Dagogo‐Jack, I., Moonsamy, P., Gainor, J. F., Lennerz, J. K., Piotrowska, Z., Lin, J. J., Lennes, I. T., Sequist, L. V. D., Shaw, A. T., Goodwin, K., et al. (2021) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2021.01.1605 · Cited by 63 · see citing works
Schoch, K., Meng, L., Szelinger, S., Bearden, D. R., Stray‐Pedersen, A., Busk, Ø. L., Stong, N., Liston, E., Cohn, R. D., Scaglia, F., et al. (2017) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2016.12.013 · Cited by 48 · see citing works
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- Authors
- Hernández‐Porras, I., Schuhmacher, A. J., Garcia‐Medina, R., Jiménez, B., Cañamero, M., de Martino, A., & Guerra, C.
- Affiliations
- Molecular Oncology Centro Nacional de Investigaciones Oncológicas (CNIO) Madrid Spain
- Spanish National Cancer Research Centre (ES)
- Biotechnology Programs Centro Nacional de Investigaciones Oncológicas (CNIO) Madrid Spain
- Corresponding author
- Guerra, Carmen
- Venue
- The Journal of Pathology
- Publisher
- Wiley
- Published
- 2016-04-26
- Volume
- 239
- Issue
- 2
- Pages
- 206-217
- ISSN
- 0022-3417 (ISSN-L)
- 1096-9896
- OpenAlex
- W2312134491
- Cited by
- 16
- References
- 52
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 3 · 2019: 1 · 2018: 2 · 2017: 2
- FWCI
- 0.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Pathology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fundación Ramón Areces (FRA 01‐09‐001)
- Instituto de Salud Carlos III
- Fundación BBVA
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Health Sciences › Medicine › Neurology › Neurofibromatosis and Schwannoma Cases
- Keywords
- Noonan syndrome, cancer susceptibility, juvenile myelomonocytic leukemia, myeloproliferative neoplasms, KRAS G12V, Trp53, pancreatitis, knock-in mice
- MeSH terms
- Alleles, Animals, Disease Models, Animal, Disease Susceptibility, Female, Heart Defects, Congenital, Genetic Carrier Screening, Humans, Lung Neoplasms, Male, Mice, Inbred C57BL, Mutation, Neoplasms, Noonan Syndrome, Oncogene Proteins, Proto-Oncogene Proteins p21(ras), Amino Acid Substitution, Mice
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