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Communication Dans Un Congrès Journal of Clinical Oncology Année : 2012

Highly sensitive determination of PIK3CA exon 9 and 20 hotspot mutations in breast tumors

Alexandre Harlé
Nicolas Lozano
  • Fonction : Auteur
Cyrielle Nicolaizeau
  • Fonction : Auteur
Maeva Lion
  • Fonction : Auteur
Marie Husson

Résumé

Background: Hotspot mutations in exons 9 (E542K and E545K) and 20 (H1047L and H1047R) of PIK3CA gene encoding for the p110α catalytic subunit of Phosphatidylinositol 3-kinases (PI3K) are found in approximately 25% of breast carcinomas. PIK3CA mutations cause the overactivation of PI3K/AKT/mTOR pathway and lead to resistance to anti-HER2 targeted therapies in breast cancers, are involved in response to anti-mTOR agents and are proposed as molecular diagnosis marker for PI3K inhibitors. A highly sensitive method is required to detect PIK3CA mutations in paraffin-embedded tumor tissues. Methods: We developed a real-time PCR assay using allele-specific scorpion primers and amplification refractory mutation system (PCR-ARMS) to detect hotspot mutations in exons 9 (E542K and E545K) and 20 (H1047L and H1047R) of PIK3CA of PI3K. Results: PIK3CA mutations were analyzed in 102 paraffin embedded breast tumors (88 invasive ductal carcinomas and 14 lobular ductal carcinomas). All specimens were validated by pathologist examination and processed for DNA extraction and PCR. PIK3CA exon 9 and 20 mutations were found in 22.5% of the specimens, 39.1% in exon 9 (26.1% for E542K, 13.0% for E545K) and 60.9% in exon 20 (17.4% for H1047L and 43.5% for H1047R). These results were comparable to the literature data (χ²=0.327 ; p<0.05). PCR ARMS was found to be highly sensitive, able to detect 0.5 % mutated DNA. Conclusion: PCR ARMS assay is highly sensitive for PIK3CA exon 9 and exon 20 hotspot mutations analysis in breast carcinomas as molecular marker for anti-HER2 and PI3K inhibitors response prediction.

Domaines

Cancer
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Dates et versions

hal-00747400 , version 1 (31-10-2012)

Identifiants

  • HAL Id : hal-00747400 , version 1

Citer

Alexandre Harlé, Nicolas Lozano, Cyrielle Nicolaizeau, Maeva Lion, Marie Husson, et al.. Highly sensitive determination of PIK3CA exon 9 and 20 hotspot mutations in breast tumors. Annual Meeting of the American Society of Clinical Oncology, ASCO'2012, Jun 2012, Chicago, Illinois, United States. pp.CDROM. ⟨hal-00747400⟩

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