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Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

5462 - Evaluation of clinicopathological and molecular criterias for screening of exonucleasic domain POLE (edPOLE) mutated patients in proficient Mismatch Repair (pMMR) colorectal and endometrial cancers.

Date

20 Oct 2018

Session

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Presenters

Justine Cohen

Citation

Annals of Oncology (2018) 29 (suppl_8): viii14-viii57. 10.1093/annonc/mdy269

Authors

J. Cohen1, B.J. Rousseau2, R. Bourgoin1, C. Tournigand2, L. Larnaudie1, A. Dupuy3, M. Ollier1, A. PUJALS1

Author affiliations

  • 1 Departement Of Pathology, Centre hospitalier universitaire Henri-Mondor, 94010 - Créteil/FR
  • 2 Service D'oncologie, Centre hospitalier universitaire Henri-Mondor, 94010 - Créteil/FR
  • 3 U955 équipe 9, INSERM, 94010 - Créteil/FR
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Resources

Abstract 5462

Background

Mismatch Repair Deficiency (dMMR) and edPOLE mutations (mt) are responsible for hypermutated tumoral phenotype. Immunotherapy have shown efficacy in dMMR/high mutation burden patients (pts) and could be also active in edPOLEmt tumors. These mt occur in 6-12% of endometrial cancers (EC) and in 1-2% of Colorectal Cancer (CRC) and are likely infrequent in advanced setting. We aimed to define the most relevant clinicopathogical and molecular criterias to facilitate screening for edPOLE mt pts.

Methods

EdPOLE mutational status was evaluated in cohorts of pMMR CRC and EC using High Resolution Melting PCR on the hotspots described in literature (codons 286, 411 and 459). CRC subcohorts were enriched for BRAF mt, RAS mt, unusual BRAF/RAS mt and young pts (≤40 yrs). Pts harboring a mutated profile were confirmed by Sanger sequencing.

Results

245 pts were screened: 49 EC and 196 CRC. Among CRC, 41 were BRAF mt (30 V600E, 11 non V600E), 79 were KRAS mt (30 on codon 12/13, 49 other mt), 20 were selected because of the presence of ≥ 2 simultaneous BRAF/KRAS/NRAS mt, 30 were BRAF/KRAS/NRAS wild type (wt) and 30 were ≤40 yrs. Using our method, 9 edPOLE mt tumors were identified (Table): 4 among EC and 5 among CRC. edPOLE mt EC were all endometrioid ADK. edPOLEmt CRC were all localized in the left colon or rectum with unusual molecular alterations: 1 BRAF (p.D594G), 3 KRAS mt (p.A59T p.A146T et p.N116H) and 1 with two NRAS mt (p.Q61R et p.T58A).Table: 109P

Tumor subcohort% of edPOLE mt (n/N)Clinical and molecular profile of edPOLE mt pts
Whole cohort3.6 (9/245)pMMR: 100% (9/9)
EC Endometrioid adenocarcinomas Other histologies8 (4/49) 13 (4/31) 0 (0/18)3 codon 286 POLE 0 codon 411 POLE 1 codon 459 POLE
CRC BRAF/KRAS/NRAS wt p.V600E BRAF mt Non p.V600E BRAF mt Codons 12 or 13 KRAS mt Non codons 12 or 13 KRAS mt Multiple BRAF/KRAS/NRAS mt2.6 (5/196) 0 (0/30) 0 (0/30) 9 (1/11) 0 (0/30) 6 (3/49) 5 (1/20)Left colon or rectum: 100% (5/5) Age ≤ 40 years old: 20% (1/5) 2 codon 286 POLE 1 codon 411 POLE 2 codon 459 POLE

Conclusions

Our screening strategy identified edPOLEmt in 13% of endometrioid ADK and 2.6% of CRC. Pts selection on clinicopathological (histology for EC, young age, left colon or rectum), and molecular criterias (pMMR, unusual BRAF/KRAS/NRAS mt) seem to increase the proportion of edPOLEmt. The use of these criteria in practice could help select patients for edPOLE screening. Additional clinicopathological and molecular data will be shown.

Clinical trial identification

Legal entity responsible for the study

Anaïs Pujals.

Funding

Has not received any funding.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.

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