{"doi":"10.1073/pnas.0900343106","title":"Endogenous expression of Hras\n                    <sup>G12V</sup>\n                    induces developmental defects and neoplasms with copy number imbalances of the oncogene","abstract":"<jats:p>\n                    We developed mice with germline endogenous expression of oncogenic\n                    <jats:italic>Hras</jats:italic>\n                    to study effects on development and mechanisms of tumor initiation. They had high perinatal mortality, abnormal cranial dimensions, defective dental ameloblasts, and nasal septal deviation, consistent with some of the features of human Costello syndrome. These mice developed papillomas and angiosarcomas, which were associated with\n                    <jats:italic>\n                      Hras\n                      <jats:sup>G12V</jats:sup>\n                    </jats:italic>\n                    allelic imbalance and augmented Hras signaling. Endogenous expression of Hras\n                    <jats:sup>G12V</jats:sup>\n                    was also associated with a higher mutation rate in vivo. Tumor initiation by Hras\n                    <jats:sup>G12V</jats:sup>\n                    likely requires augmentation of signal output, which in papillomas and angiosarcomas is achieved via increased\n                    <jats:italic>Hras</jats:italic>\n                    -gene copy number, which may be favored by a higher mutation frequency in cells expressing the oncoprotein.\n                  </jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2009,"id":613407,"datarank":0.7423139835567254,"base_score":4.948759890378168,"endowment":4.948759890378168,"self_citation_contribution":0.7423139835567254,"citation_network_contribution":0.0,"self_endowment_contribution":0.7423139835567254,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":140,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":802164,"name":"Norisato Mitsutake","orcid":"0000-0002-2744-8046","position":1,"is_corresponding":false},{"id":829880,"name":"Krista LaPerle","orcid":null,"position":2,"is_corresponding":false},{"id":626941,"name":"Nagako Akeno","orcid":null,"position":3,"is_corresponding":false},{"id":345009,"name":"Pat Zanzonico","orcid":"0000-0002-7334-2752","position":4,"is_corresponding":false},{"id":478740,"name":"Valerie A. Longo","orcid":"0000-0002-0155-0050","position":5,"is_corresponding":false},{"id":1580294,"name":"Shin Mitsutake","orcid":null,"position":6,"is_corresponding":false},{"id":1580296,"name":"Edna T. Kimura","orcid":null,"position":7,"is_corresponding":false},{"id":313671,"name":"Hartmut Geiger","orcid":"0000-0002-5794-5430","position":8,"is_corresponding":false},{"id":1580298,"name":"Eugenio Santos","orcid":null,"position":9,"is_corresponding":false},{"id":1580300,"name":"Hans G. Wendel","orcid":null,"position":10,"is_corresponding":false},{"id":1580301,"name":"Aime Franco","orcid":null,"position":11,"is_corresponding":false},{"id":277160,"name":"Jeffrey A. Knauf","orcid":"0000-0003-4456-8792","position":12,"is_corresponding":false},{"id":108810,"name":"James A. Fagin","orcid":"0000-0002-2365-2517","position":13,"is_corresponding":false},{"id":1321533,"name":"Xu Chen","orcid":"0000-0001-8322-6133","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Endogenous expression of Hras\n                    <sup>G12V</sup>\n                    induces developmental defects and neoplasms with copy number imbalances of the oncogene","abstract":"<jats:p>\n                    We developed mice with germline endogenous expression of oncogenic\n                    <jats:italic>Hras</jats:italic>\n                    to study effects on development and mechanisms of tumor initiation. They had high perinatal mortality, abnormal cranial dimensions, defective dental ameloblasts, and nasal septal deviation, consistent with some of the features of human Costello syndrome. These mice developed papillomas and angiosarcomas, which were associated with\n                    <jats:italic>\n                      Hras\n                      <jats:sup>G12V</jats:sup>\n                    </jats:italic>\n                    allelic imbalance and augmented Hras signaling. Endogenous expression of Hras\n                    <jats:sup>G12V</jats:sup>\n                    was also associated with a higher mutation rate in vivo. Tumor initiation by Hras\n                    <jats:sup>G12V</jats:sup>\n                    likely requires augmentation of signal output, which in papillomas and angiosarcomas is achieved via increased\n                    <jats:italic>Hras</jats:italic>\n                    -gene copy number, which may be favored by a higher mutation frequency in cells expressing the oncoprotein.\n                  </jats:p>","is_dataset_classified":null,"base_score":4.948759890378168,"endowment":4.948759890378168,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19416908","pmcid":"PMC2674938","openalex_id":"https://openalex.org/W1990899188","authors":[],"funders":[{"funder_name":"NCI NIH HHS","grant_id":"P30 CA08748","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R24 CA83084","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R24 CA083084","title":null},{"funder_name":"NCI NIH HHS","grant_id":"CA72597","title":null},{"funder_name":"NCI NIH HHS","grant_id":"P30 CA008748","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA050706","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"T32 DK007313","title":null},{"funder_name":"NCI NIH HHS","grant_id":"CA50706","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"T32 DK07313","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA072597","title":null}],"total_grants":10,"fwci":2.1417,"citation_percentile":0.86805004,"influential_citations":0,"citation_trend":[{"year":2012,"count":2},{"year":2013,"count":9},{"year":2014,"count":5},{"year":2015,"count":16},{"year":2016,"count":8},{"year":2017,"count":13},{"year":2018,"count":6},{"year":2019,"count":8},{"year":2020,"count":6},{"year":2021,"count":20},{"year":2022,"count":8},{"year":2023,"count":3},{"year":2024,"count":11},{"year":2025,"count":7},{"year":2026,"count":3}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2674938","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2674938","host_type":"repository"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.0900343106","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.0900343106","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/19416908","host_type":"repository"}],"fields_of_study":["Protein Tyrosine Phosphatases","Infectious Diseases and Mycology","Developmental Biology and Gene Regulation"],"mesh_terms":["Alleles","Animals","DNA Mutational Analysis","Immunohistochemistry","Mice, Transgenic","Mutation","Neoplasms","Oncogenes","Tomography, X-Ray Computed","Signal Transduction","Gene Expression Regulation, Neoplastic","Gene Expression Regulation, Developmental","ras Proteins","Genetic Predisposition to Disease","Mice"],"keywords":["HRAS","Endogeny","Mutation","Cancer research","Biology","Germline mutation","Germline","Oncogene","Allele","Genetics","Gene","Endocrinology","Cell cycle"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-02T07:58:40.956338Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}