Variants-Mutants

• IDH1-R132H
  25 February 2015

  Tumors
  gliomas
  low-grade glioma
  diffuse astrocytoma
  acute myelogenous leukemia (AML)
  gastrointestinal cancer
  Decreased expression of IDH1-R132H correlates with poor survival in gastrointestinal cancer. (#27655638#)
  Immunochemistry
  IHC for IDH1-R132H is relatively sensitive and specific, but there is a discordance rate that is not trivial, with NGS mutation profiling. In addition, a significant proportion of patients harbor IDH1 non-R132H mutations not detectable by IHC, (...)

• KRAS-G13D
  20 August 2014

  Mutation in codon 12 or 13 in the Kirsten rat sarcoma viral oncogene homolog (KRAS) gene, downstream of the EGFR, evokes constitutive activation of the RAS/RAF/MAPK signaling pathway and correlates with resistance to anti-EGFR monoclonal antibody (mAb) therapies.
  However, a retrospective study reported that a proportion of patients with the KRAS G13D mutation may respond to cetuximab. A similar analysis for panitumumab was not as conclusive.
  In a cell line study (#24558511#), After (...)

• BCR-ABL-T315I
  22 September 2013

  T315I gatekeeper mutation in the Bcr-Abl tyrosine kinase
  Despite the remarkable success of imatinib against Bcr-Abl, development of secondary resistance, most often due to point mutations in the Bcr-Abl tyrosine kinase (TK) domain, is quite common.
  Of these, the T315I "gatekeeper" mutation is resistant to all currently registered Bcr-Abl TK inhibitors (TKIs) with the notable exception of ponatinib (Iclusig™), which was approved by the United States Food and Drug Administration (FDA). (...)

• EGFR-exon 20 mutations
  28 June 2013

  EGFR-exon 20 insertions
  In contrast to other primary epidermal growth factor receptor (EGFR) mutations in lung adenocarcinomas, insertions in exon 20 of EGFR have been generally associated with resistance to EGFR-tyrosine kinase inhibitors.
  EGFR exon 20 insertion testing identifies a distinct subset of lung adenocarcinomas, accounting for at least 9% of all EGFR-mutated cases, representing the third most common type of EGFR mutation after exon 19 deletions and L858R.
  Insertions are (...)

• EGFR-G719X
  28 June 2013

  ’Classical’ mutations in the EGFR tyrosine kinase domain (exons 18, 19 and 21) have been associated with sensitivity to tyrosine kinase inhibitors (TKIs) in patients with NSCLC.
  These classical mutations are : G719X, DEL19 and L858R mutations and confer sensitivity to TKIs.

• EGFR-L858R
  25 June 2013

  EGFR c.2573T>G MCG
  Patients with lung cancer who respond to gefitinib have been reported to have somatic mutations consisting of deletions in exon 19 and the L858R mutation in exon 21 of the epidermal growth factor receptor (EGFR) gene.
  Lung cancers harboring the EGFR L858R mutation have been reported to be responsive to gefitinib.
  The studies of cells expressing L858R revealed increased gefitinib sensitivity in vitro.
  Associations
  A patient with gefitinib-resistant lung (...)

• PIK3CA-Q546P
  10 December 2012

  References
  Biphasic Papillary and Lobular Breast Carcinoma With PIK3CA and IDH1 Mutations. Ang D, Vansandt AM, Beadling C, Warrick A, West RB, Corless CL, Troxell ML. Diagn Mol Pathol. 2012 Dec;21(4):221-4. PMID: #23111200#

• PIK3CA-H1047R
  10 December 2012

  References
  Biphasic Papillary and Lobular Breast Carcinoma With PIK3CA and IDH1 Mutations. Ang D, Vansandt AM, Beadling C, Warrick A, West RB, Corless CL, Troxell ML. Diagn Mol Pathol. 2012 Dec;21(4):221-4. PMID: #23111200#

• EGFR-T790M
  4 April 2012

  The T790M mutation was shown to confer resistance to gefitinib after it was introduced into the sequence of the wild-type EGFR and L858R mutant EGFR in vitro.
  The T790M mutation results in steric hindrance of binding of gefitinib to the ATP-kinase–binding pocket.
  Targeted therapy
  third-generation epidermal growth factor receptor (EGFR ) tyrosine kinase inhibitor (TKIs )
  rociletinib
  osimertinib
  References
  Sequist LV, Goldman JW, Wakelee HA, et al. Efficacy of rociletinib (CO-1686) (...)

• JAK2 exon 12 mutations
  7 December 2011

  Pathology
  polycythemia vera JAK2(V617F) JAK2 exon 12 mutations. N542-E543del mutation R541-E543delinsK
  No evidence for JAK2 exon 12 mutations in primary mediastinal large B-cell lymphoma. (#19704259#)
  References
  No evidence for the JAK2 (V617F) or JAK2 exon 12 mutations in primary mediastinal large B-cell lymphoma. Wu D, Dutra B, Lindeman N, Takahashi H, Takeyama K, Harris NL, Pinkus GS, Longtine J, Shipp M, Kutok JL. Diagn Mol Pathol. 2009 Sep;18(3):144-9. PMID: #19704259# (Free) (...)

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