KRAS mutation
Revision as of 13:08, 10 October 2017 by Jensflorian (talk | contribs) (→Implication: heterogeneity)
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:
- Invasive ductal carcinoma of the pancreas.
- Colorectal carcinoma.[2]
- lung adenocarcinomas (approx 30%)[3]
- squamous NSCLC (~5%)
Not seen in the context of:
- ALK rearrangements in non-small cell lung cancer.[4]
- Almost mutually exclusive to BRAF (V600E) in colon cancer.[5]
Implication
In the context of colorectal carcinoma:[6][7]
- Patient must have wild type KRAS to get drugs; KRAS mutation predicts resistance to cetuximab (Erbitux) and panitumumab (Vectibix).
- KRAS mutations are usually stable between primary and metastatic tumors. [8]
In the context of lung cancer:[9]
- Mutations are rare in never-smokers.
- Biomarker for MEK inhibitors selumetinib and trametinib.
Gross
In colorectal carcinoma:
- Typically right sided lesions.[5]
Microscopic
Features:
- In lung adenocarcinoma:
- Typically mucinous carcinoma.[10]
- Associated with tumour-infiltrating leukocytes.[11]
- In colorectal carcinoma:
See also
References
- ↑ Online 'Mendelian Inheritance in Man' (OMIM) 190070
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 5.0 5.1 5.2 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.