Difference between revisions of "KRAS mutation"

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In the context of colorectal carcinoma:<ref name=pmid20956938>{{cite journal |author=Dunn EF, Iida M, Myers RA, ''et al.'' |title=Dasatinib sensitizes KRAS mutant colorectal tumors to cetuximab |journal=Oncogene |volume= |issue= |pages= |year=2010 |month=October |pmid=20956938 |doi=10.1038/onc.2010.430 |url=}}</ref><ref name=pmid19001320>{{cite journal |author=Di Nicolantonio F, Martini M, Molinari F, ''et al.'' |title=Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer |journal=J. Clin. Oncol. |volume=26 |issue=35 |pages=5705–12 |year=2008 |month=December |pmid=19001320 |doi=10.1200/JCO.2008.18.0786 |url=}}</ref>
In the context of colorectal carcinoma:<ref name=pmid20956938>{{cite journal |author=Dunn EF, Iida M, Myers RA, ''et al.'' |title=Dasatinib sensitizes KRAS mutant colorectal tumors to cetuximab |journal=Oncogene |volume= |issue= |pages= |year=2010 |month=October |pmid=20956938 |doi=10.1038/onc.2010.430 |url=}}</ref><ref name=pmid19001320>{{cite journal |author=Di Nicolantonio F, Martini M, Molinari F, ''et al.'' |title=Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer |journal=J. Clin. Oncol. |volume=26 |issue=35 |pages=5705–12 |year=2008 |month=December |pmid=19001320 |doi=10.1200/JCO.2008.18.0786 |url=}}</ref>
*Patient must have ''wild type'' KRAS to get drugs; KRAS mutation predicts resistance to [[cetuximab]] (Erbitux) and [[panitumumab]] (Vectibix).
*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. <ref>{{Cite journal  | last1 = Petaccia de Macedo | first1 = M. | last2 = Melo | first2 = FM. | last3 = Ribeiro | first3 = HSC. | last4 = Marques | first4 = MC. | last5 = Kagohara | first5 = LT. | last6 = Begnami | first6 = MD. | last7 = Neto | first7 = JC. | last8 = Ribeiro | first8 = JS. | last9 = Soares | first9 = FA. | title = 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. | journal = Am J Cancer Res | volume = 7 | issue = 9 | pages = 1978-1989 | month =  | year = 2017 | doi =  | PMID = 28979819 }}</ref>
In the context of lung cancer:<ref>{{Cite journal  | last1 = Riely | first1 = GJ. | last2 = Kris | first2 = MG. | last3 = Rosenbaum | first3 = D. | last4 = Marks | first4 = J. | last5 = Li | first5 = A. | last6 = Chitale | first6 = DA. | last7 = Nafa | first7 = K. | last8 = Riedel | first8 = ER. | last9 = Hsu | first9 = M. | title = Frequency and distinctive spectrum of KRAS mutations in never smokers with lung adenocarcinoma. | journal = Clin Cancer Res | volume = 14 | issue = 18 | pages = 5731-4 | month = Sep | year = 2008 | doi = 10.1158/1078-0432.CCR-08-0646 | PMID = 18794081 }}</ref>
In the context of lung cancer:<ref>{{Cite journal  | last1 = Riely | first1 = GJ. | last2 = Kris | first2 = MG. | last3 = Rosenbaum | first3 = D. | last4 = Marks | first4 = J. | last5 = Li | first5 = A. | last6 = Chitale | first6 = DA. | last7 = Nafa | first7 = K. | last8 = Riedel | first8 = ER. | last9 = Hsu | first9 = M. | title = Frequency and distinctive spectrum of KRAS mutations in never smokers with lung adenocarcinoma. | journal = Clin Cancer Res | volume = 14 | issue = 18 | pages = 5731-4 | month = Sep | year = 2008 | doi = 10.1158/1078-0432.CCR-08-0646 | PMID = 18794081 }}</ref>
* Mutations are rare in never-smokers.
* Mutations are rare in never-smokers.

Revision as of 13:08, 10 October 2017

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

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:

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. ↑ 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.
  4. ↑ 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. ↑ 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.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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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