KRAS mutation

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KRAS mutation is a re-occuring theme in molecular pathology. KRAS is an oncogene.[1]

General

Kirsten RAS (KRAS) is a member of the Ras gene familiy, which encodes small G proteins with intrinsic GTPase activity.

Seen in:

Not seen in the context of:

Implication

Colorectal cancer

In the context of colorectal carcinoma:[8][9]

  • Patient must have wild type KRAS to get drugs; KRAS mutation predicts resistance to cetuximab (Erbitux) and panitumumab (Vectibix).
  • The vast majority of activating mutations are found in codon 12/13, 61 and 146.[10]
  • KRAS mutations are usually stable between primary and metastatic tumors. [11]
  • KRAS mutation predict poor response to FOLFOX treatment.[12]

Lung cancer

In the context of lung cancer:[13]

  • Mutations are rare in never-smokers.
  • KRAS G12C is the most common G > T transversion mutation in smokers.[14]
  • Biomarker for MEK inhibitors selumetinib and trametinib.

Gross

In colorectal carcinoma:

  • Typically right sided lesions.[7]

Microscopic

Features:

See also

References

  1. ↑ Online 'Mendelian Inheritance in Man' (OMIM) 190070
  2. ↑ Monzon, FA.; Ogino, S.; Hammond, ME.; Halling, KC.; Bloom, KJ.; Nikiforova, MN. (Oct 2009). "The role of KRAS mutation testing in the management of patients with metastatic colorectal cancer.". Arch Pathol Lab Med 133 (10): 1600-6. doi:10.1043/1543-2165-133.10.1600. PMID 19792050.
  3. ↑ Imamura, Y.; Lochhead, P.; Yamauchi, M.; Kuchiba, A.; Qian, ZR.; Liao, X.; Nishihara, R.; Jung, S. et al. (May 2014). "Analyses of clinicopathological, molecular, and prognostic associations of KRAS codon 61 and codon 146 mutations in colorectal cancer: cohort study and literature review.". Mol Cancer 13: 135. doi:10.1186/1476-4598-13-135. PMID 24885062.
  4. ↑ Korpanty, GJ.; Graham, DM.; Vincent, MD.; Leighl, NB. (2014). "Biomarkers That Currently Affect Clinical Practice in Lung Cancer: EGFR, ALK, MET, ROS-1, and KRAS.". Front Oncol 4: 204. doi:10.3389/fonc.2014.00204. PMID 25157335.
  5. ↑ Cuatrecasas, M.; Villanueva, A.; Matias-Guiu, X.; Prat, J. (Apr 1997). "K-ras mutations in mucinous ovarian tumors: a clinicopathologic and molecular study of 95 cases.". Cancer 79 (8): 1581-6. PMID 9118042.
  6. ↑ Gainor, JF.; Varghese, AM.; Ou, SH.; Kabraji, S.; Awad, MM.; Katayama, R.; Pawlak, A.; Mino-Kenudson, M. et al. (Aug 2013). "ALK rearrangements are mutually exclusive with mutations in EGFR or KRAS: an analysis of 1,683 patients with non-small cell lung cancer.". Clin Cancer Res 19 (15): 4273-81. doi:10.1158/1078-0432.CCR-13-0318. PMID 23729361.
  7. ↑ 7.0 7.1 7.2 Gonsalves, WI.; Mahoney, MR.; Sargent, DJ.; Nelson, GD.; Alberts, SR.; Sinicrope, FA.; Goldberg, RM.; Limburg, PJ. et al. (Jul 2014). "Patient and tumor characteristics and BRAF and KRAS mutations in colon cancer, NCCTG/Alliance N0147.". J Natl Cancer Inst 106 (7). doi:10.1093/jnci/dju106. PMID 24925349.
  8. ↑ Dunn EF, Iida M, Myers RA, et al. (October 2010). "Dasatinib sensitizes KRAS mutant colorectal tumors to cetuximab". Oncogene. doi:10.1038/onc.2010.430. PMID 20956938.
  9. ↑ Di Nicolantonio F, Martini M, Molinari F, et al. (December 2008). "Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer". J. Clin. Oncol. 26 (35): 5705–12. doi:10.1200/JCO.2008.18.0786. PMID 19001320.
  10. ↑ Imamura, Y.; Lochhead, P.; Yamauchi, M.; Kuchiba, A.; Qian, ZR.; Liao, X.; Nishihara, R.; Jung, S. et al. (May 2014). "Analyses of clinicopathological, molecular, and prognostic associations of KRAS codon 61 and codon 146 mutations in colorectal cancer: cohort study and literature review.". Mol Cancer 13: 135. doi:10.1186/1476-4598-13-135. PMID 24885062.
  11. ↑ Petaccia de Macedo, M.; Melo, FM.; Ribeiro, HSC.; Marques, MC.; Kagohara, LT.; Begnami, MD.; Neto, JC.; Ribeiro, JS. et al. (2017). "KRAS mutation status is highly homogeneous between areas of the primary tumor and the corresponding metastasis of colorectal adenocarcinomas: one less problem in patient care.". Am J Cancer Res 7 (9): 1978-1989. PMID 28979819.
  12. ↑ Zocche, DM.; Ramirez, C.; Fontao, FM.; Costa, LD.; Redal, MA. (2015). "Global impact of KRAS mutation patterns in FOLFOX treated metastatic colorectal cancer.". Front Genet 6: 116. doi:10.3389/fgene.2015.00116. PMID 25870609.
  13. ↑ Riely, GJ.; Kris, MG.; Rosenbaum, D.; Marks, J.; Li, A.; Chitale, DA.; Nafa, K.; Riedel, ER. et al. (Sep 2008). "Frequency and distinctive spectrum of KRAS mutations in never smokers with lung adenocarcinoma.". Clin Cancer Res 14 (18): 5731-4. doi:10.1158/1078-0432.CCR-08-0646. PMID 18794081.
  14. ↑ Dogan, S.; Shen, R.; Ang, DC.; Johnson, ML.; D'Angelo, SP.; Paik, PK.; Brzostowski, EB.; Riely, GJ. et al. (Nov 2012). "Molecular epidemiology of EGFR and KRAS mutations in 3,026 lung adenocarcinomas: higher susceptibility of women to smoking-related KRAS-mutant cancers.". Clin Cancer Res 18 (22): 6169-77. doi:10.1158/1078-0432.CCR-11-3265. PMID 23014527.
  15. ↑ Kadota, K.; Yeh, YC.; D'Angelo, SP.; Moreira, AL.; Kuk, D.; Sima, CS.; Riely, GJ.; Arcila, ME. et al. (Aug 2014). "Associations between mutations and histologic patterns of mucin in lung adenocarcinoma: invasive mucinous pattern and extracellular mucin are associated with KRAS mutation.". Am J Surg Pathol 38 (8): 1118-27. doi:10.1097/PAS.0000000000000246. PMID 25029118.
  16. ↑ Rekhtman, N.; Ang, DC.; Riely, GJ.; Ladanyi, M.; Moreira, AL. (Oct 2013). "KRAS mutations are associated with solid growth pattern and tumor-infiltrating leukocytes in lung adenocarcinoma.". Mod Pathol 26 (10): 1307-19. doi:10.1038/modpathol.2013.74. PMID 23619604.
  17. ↑ Gao, J.; Zhang, J.; Lu, T.; Li, XY.; Jia, N.; Liang, ZY. (Sep 2012). "[Correlation between KRAS mutations and clinicopathologic features in colorectal carcinomas].". Zhonghua Bing Li Xue Za Zhi 41 (9): 595-8. PMID 23157826.
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