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Activating KRAS Exon 3 Mutation

MedGen UID:
1722691
•Concept ID:
C5420205
•
Cell or Molecular Dysfunction
Synonyms: Activating c-K-ras Exon 3 Mutation; Activating KRAS Exon 3 Gene Mutation; Activating KRAS-2 Exon 3 Mutation; Activating KRAS2 Exon 3 Mutation; Activating v-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog Exon 3 Mutation; KRAS Exon 3 Activating Gene Mutation; KRAS Exon 3 Activating Mutation

Definition

A change in the nucleotide sequence of exon 3 of the KRAS gene that results in constitutive activation of both GTPase KRas protein and its downstream signaling pathways. [from NCI]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVActivating KRAS Exon 3 Mutation

Professional guidelines

PubMed

Concurrent gene alterations with EGFR mutation and treatment efficacy of EGFR-TKIs in Chinese patients with non-small cell lung cancer.
Hu W, Liu Y, Chen J
Oncotarget 2017 Apr 11;8(15):25046-25054. doi: 10.18632/oncotarget.15337. PMID: 28212572Free PMC Article
Improved risk assessment of endometrial cancer by combined analysis of MSI, PI3K-AKT, Wnt/β-catenin and P53 pathway activation.
Nout RA, Bosse T, Creutzberg CL, Jürgenliemk-Schulz IM, Jobsen JJ, Lutgens LC, van der Steen-Banasik EM, van Eijk R, Ter Haar NT, Smit VT
Gynecol Oncol 2012 Sep;126(3):466-73. Epub 2012 May 15 doi: 10.1016/j.ygyno.2012.05.012. PMID: 22609107
Spectrum of MEK1 and MEK2 gene mutations in cardio-facio-cutaneous syndrome and genotype-phenotype correlations.
Dentici ML, Sarkozy A, Pantaleoni F, Carta C, Lepri F, Ferese R, Cordeddu V, Martinelli S, Briuglia S, Digilio MC, Zampino G, Tartaglia M, Dallapiccola B
Eur J Hum Genet 2009 Jun;17(6):733-40. Epub 2009 Jan 21 doi: 10.1038/ejhg.2008.256. PMID: 19156172Free PMC Article

Recent clinical studies

Etiology

Different prognostic values of KRAS exon 2 submutations and BRAF V600E mutation in microsatellite stable (MSS) and unstable (MSI) stage III colon cancer: an ACCENT/IDEA pooled analysis of seven trials.
Taieb J, Sinicrope FA, Pederson L, Lonardi S, Alberts SR, George TJ, Yothers G, Van Cutsem E, Saltz L, Ogino S, Kerr R, Yoshino T, Goldberg RM, André T, Laurent-Puig P, Shi Q
Ann Oncol 2023 Nov;34(11):1025-1034. Epub 2023 Aug 23 doi: 10.1016/j.annonc.2023.08.006. PMID: 37619846Free PMC Article
Osimertinib As First-Line Treatment of EGFR Mutation-Positive Advanced Non-Small-Cell Lung Cancer.
Ramalingam SS, Yang JC, Lee CK, Kurata T, Kim DW, John T, Nogami N, Ohe Y, Mann H, Rukazenkov Y, Ghiorghiu S, Stetson D, Markovets A, Barrett JC, Thress KS, Jänne PA
J Clin Oncol 2018 Mar 20;36(9):841-849. Epub 2017 Aug 25 doi: 10.1200/JCO.2017.74.7576. PMID: 28841389
MET Exon 14 Mutations in Non-Small-Cell Lung Cancer Are Associated With Advanced Age and Stage-Dependent MET Genomic Amplification and c-Met Overexpression.
Awad MM, Oxnard GR, Jackman DM, Savukoski DO, Hall D, Shivdasani P, Heng JC, Dahlberg SE, Jänne PA, Verma S, Christensen J, Hammerman PS, Sholl LM
J Clin Oncol 2016 Mar 1;34(7):721-30. Epub 2016 Jan 4 doi: 10.1200/JCO.2015.63.4600. PMID: 26729443
Fluorouracil, leucovorin, and irinotecan plus cetuximab treatment and RAS mutations in colorectal cancer.
Van Cutsem E, Lenz HJ, Köhne CH, Heinemann V, Tejpar S, Melezínek I, Beier F, Stroh C, Rougier P, van Krieken JH, Ciardiello F
J Clin Oncol 2015 Mar 1;33(7):692-700. Epub 2015 Jan 20 doi: 10.1200/JCO.2014.59.4812. PMID: 25605843
Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer.
Douillard JY, Oliner KS, Siena S, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocákova I, Ruff P, Błasińska-Morawiec M, Šmakal M, Canon JL, Rother M, Williams R, Rong A, Wiezorek J, Sidhu R, Patterson SD
N Engl J Med 2013 Sep 12;369(11):1023-34. doi: 10.1056/NEJMoa1305275. PMID: 24024839

Diagnosis

Exploring the Relationship Between KRAS, NRAS, and BRAF Mutations and Clinical Characteristics in Iranian Colorectal Cancer Patients.
Mosaferi Z, Pirestani M, Arefian E, Gojani G, Kavousinasab N, Karimi P, Deilami A, Abrehdari-Tafreshi Z
J Gastrointest Cancer 2024 Sep;55(3):1134-1143. Epub 2024 May 6 doi: 10.1007/s12029-024-01064-0. PMID: 38709419
High frequency of hotspot mutation in PTPN11 gene among Moroccan patients with Noonan syndrome.
Ouboukss F, Adadi N, Amasdl S, Smaili W, Laarabi FZ, Lyahyai J, Sefiani A, Ratbi I
J Appl Genet 2024 May;65(2):303-308. Epub 2023 Nov 21 doi: 10.1007/s13353-023-00803-6. PMID: 37987971
High frequency of BRAF mutations in primary mucinous ovarian carcinoma of Taiwanese patients.
Chao WR, Lee YJ, Lee MY, Sheu GT, Han CP
Taiwan J Obstet Gynecol 2021 Nov;60(6):1072-1077. doi: 10.1016/j.tjog.2021.09.019. PMID: 34794740
Effect of KRAS exon 2 mutations on antitumor activity of afatinib and gefitinib.
Gamba S, Camaj P, Heinemann V, Laubender RP, Wang Y, Zhao Y, Stintzing S, Giessen C, Boeck S, Haertl C, Bruns CJ, Modest DP
Anticancer Drugs 2015 Apr;26(4):371-8. doi: 10.1097/CAD.0000000000000196. PMID: 25514114
Mutation status of somatic EGFR and KRAS genes in Chinese patients with prostate cancer (PCa).
Fu M, Zhang W, Shan L, Song J, Shang D, Ying J, Zhao J
Virchows Arch 2014 May;464(5):575-81. Epub 2014 Mar 5 doi: 10.1007/s00428-014-1566-x. PMID: 24595526

Therapy

Different prognostic values of KRAS exon 2 submutations and BRAF V600E mutation in microsatellite stable (MSS) and unstable (MSI) stage III colon cancer: an ACCENT/IDEA pooled analysis of seven trials.
Taieb J, Sinicrope FA, Pederson L, Lonardi S, Alberts SR, George TJ, Yothers G, Van Cutsem E, Saltz L, Ogino S, Kerr R, Yoshino T, Goldberg RM, André T, Laurent-Puig P, Shi Q
Ann Oncol 2023 Nov;34(11):1025-1034. Epub 2023 Aug 23 doi: 10.1016/j.annonc.2023.08.006. PMID: 37619846Free PMC Article
Osimertinib As First-Line Treatment of EGFR Mutation-Positive Advanced Non-Small-Cell Lung Cancer.
Ramalingam SS, Yang JC, Lee CK, Kurata T, Kim DW, John T, Nogami N, Ohe Y, Mann H, Rukazenkov Y, Ghiorghiu S, Stetson D, Markovets A, Barrett JC, Thress KS, Jänne PA
J Clin Oncol 2018 Mar 20;36(9):841-849. Epub 2017 Aug 25 doi: 10.1200/JCO.2017.74.7576. PMID: 28841389
MET Exon 14 Mutations in Non-Small-Cell Lung Cancer Are Associated With Advanced Age and Stage-Dependent MET Genomic Amplification and c-Met Overexpression.
Awad MM, Oxnard GR, Jackman DM, Savukoski DO, Hall D, Shivdasani P, Heng JC, Dahlberg SE, Jänne PA, Verma S, Christensen J, Hammerman PS, Sholl LM
J Clin Oncol 2016 Mar 1;34(7):721-30. Epub 2016 Jan 4 doi: 10.1200/JCO.2015.63.4600. PMID: 26729443
Fluorouracil, leucovorin, and irinotecan plus cetuximab treatment and RAS mutations in colorectal cancer.
Van Cutsem E, Lenz HJ, Köhne CH, Heinemann V, Tejpar S, Melezínek I, Beier F, Stroh C, Rougier P, van Krieken JH, Ciardiello F
J Clin Oncol 2015 Mar 1;33(7):692-700. Epub 2015 Jan 20 doi: 10.1200/JCO.2014.59.4812. PMID: 25605843
Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer.
Douillard JY, Oliner KS, Siena S, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocákova I, Ruff P, Błasińska-Morawiec M, Šmakal M, Canon JL, Rother M, Williams R, Rong A, Wiezorek J, Sidhu R, Patterson SD
N Engl J Med 2013 Sep 12;369(11):1023-34. doi: 10.1056/NEJMoa1305275. PMID: 24024839

Prognosis

Targeted therapeutic options in early and metastatic NSCLC-overview.
Gálffy G, Morócz É, Korompay R, Hécz R, Bujdosó R, Puskás R, Lovas T, Gáspár E, Yahya K, Király P, Lohinai Z
Pathol Oncol Res 2024;30:1611715. Epub 2024 Mar 28 doi: 10.3389/pore.2024.1611715. PMID: 38605928Free PMC Article
Different prognostic values of KRAS exon 2 submutations and BRAF V600E mutation in microsatellite stable (MSS) and unstable (MSI) stage III colon cancer: an ACCENT/IDEA pooled analysis of seven trials.
Taieb J, Sinicrope FA, Pederson L, Lonardi S, Alberts SR, George TJ, Yothers G, Van Cutsem E, Saltz L, Ogino S, Kerr R, Yoshino T, Goldberg RM, André T, Laurent-Puig P, Shi Q
Ann Oncol 2023 Nov;34(11):1025-1034. Epub 2023 Aug 23 doi: 10.1016/j.annonc.2023.08.006. PMID: 37619846Free PMC Article
Osimertinib As First-Line Treatment of EGFR Mutation-Positive Advanced Non-Small-Cell Lung Cancer.
Ramalingam SS, Yang JC, Lee CK, Kurata T, Kim DW, John T, Nogami N, Ohe Y, Mann H, Rukazenkov Y, Ghiorghiu S, Stetson D, Markovets A, Barrett JC, Thress KS, Jänne PA
J Clin Oncol 2018 Mar 20;36(9):841-849. Epub 2017 Aug 25 doi: 10.1200/JCO.2017.74.7576. PMID: 28841389
RAS proto-oncogene in medullary thyroid carcinoma.
Moura MM, Cavaco BM, Leite V
Endocr Relat Cancer 2015 Oct;22(5):R235-52. doi: 10.1530/ERC-15-0070. PMID: 26285815
Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer.
Douillard JY, Oliner KS, Siena S, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocákova I, Ruff P, Błasińska-Morawiec M, Šmakal M, Canon JL, Rother M, Williams R, Rong A, Wiezorek J, Sidhu R, Patterson SD
N Engl J Med 2013 Sep 12;369(11):1023-34. doi: 10.1056/NEJMoa1305275. PMID: 24024839

Clinical prediction guides

Different prognostic values of KRAS exon 2 submutations and BRAF V600E mutation in microsatellite stable (MSS) and unstable (MSI) stage III colon cancer: an ACCENT/IDEA pooled analysis of seven trials.
Taieb J, Sinicrope FA, Pederson L, Lonardi S, Alberts SR, George TJ, Yothers G, Van Cutsem E, Saltz L, Ogino S, Kerr R, Yoshino T, Goldberg RM, André T, Laurent-Puig P, Shi Q
Ann Oncol 2023 Nov;34(11):1025-1034. Epub 2023 Aug 23 doi: 10.1016/j.annonc.2023.08.006. PMID: 37619846Free PMC Article
Crizotinib in Patients With MET-Amplified NSCLC.
Camidge DR, Otterson GA, Clark JW, Ignatius Ou SH, Weiss J, Ades S, Shapiro GI, Socinski MA, Murphy DA, Conte U, Tang Y, Wang SC, Wilner KD, Villaruz LC
J Thorac Oncol 2021 Jun;16(6):1017-1029. Epub 2021 Mar 4 doi: 10.1016/j.jtho.2021.02.010. PMID: 33676017
MET Exon 14 Mutations in Non-Small-Cell Lung Cancer Are Associated With Advanced Age and Stage-Dependent MET Genomic Amplification and c-Met Overexpression.
Awad MM, Oxnard GR, Jackman DM, Savukoski DO, Hall D, Shivdasani P, Heng JC, Dahlberg SE, Jänne PA, Verma S, Christensen J, Hammerman PS, Sholl LM
J Clin Oncol 2016 Mar 1;34(7):721-30. Epub 2016 Jan 4 doi: 10.1200/JCO.2015.63.4600. PMID: 26729443
Overcoming Resistance to Anti-EGFR Therapy in Colorectal Cancer.
Dienstmann R, Salazar R, Tabernero J
Am Soc Clin Oncol Educ Book 2015:e149-56. doi: 10.14694/EdBook_AM.2015.35.e149. PMID: 25993166
Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer.
Douillard JY, Oliner KS, Siena S, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocákova I, Ruff P, Błasińska-Morawiec M, Šmakal M, Canon JL, Rother M, Williams R, Rong A, Wiezorek J, Sidhu R, Patterson SD
N Engl J Med 2013 Sep 12;369(11):1023-34. doi: 10.1056/NEJMoa1305275. PMID: 24024839

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