FL

AACR 2017 poster 2444/1 – Recurrent mutations and clinical outcomes in patients with Follicular Lymphoma

On Monday 3rd April during this year’s American Association for Cancer Research (AACR) annual meeting, a poster (2444 / 1) by Kilannin Krysiak, from Washington University, St. Louis, MO, et al. titled “Recurrent mutations and clinical outcomes in patients with follicular lymphoma” was presented.

The group aimed to validate previously found mutations and to identify clinically relevant mutations in FL. They designed a large, custom capture lymphoma-related gene panel and queried 113 samples from mostly newly diagnosed FL patients.

Key Highlights:
  • From 105 patients, 39 significantly mutated genes (SMGs) were identified
  • This included previously known genes in FL: KMT2D, EZH2, TNFRSF14
  • Identified novel mutations: BTK, HVCN1
  • 110 CREBBP mutations
  • Significant co-occurrence of histone family mutations reported (P = 0.0001); 46 patients harbored >1 histone family mutation
  • Twenty-three patients (22%) had genetic aberrations likely to up-regulate signaling downstream of BTK, possible altering response rates to BTK-specific therapy
  • In patients sequenced within 12 months of first-line therapy (n = 59), those with HVCN1 mutations had improved PFS (P < 0.05) whereas those with CREBBP mutations had a significantly poorer PFS (P < 0.05)
  • Sequencing of an additional 199 FL samples found 14 TNFAIP3 truncating, 18 CARD11 coiled-coil domain, 4 BCL10 truncating, and 8 BTK mutations
  • These mutations affected 18.4% of patients in this cohort, and potentially upregulate NFkB signaling and may impact ibrutinib sensitivity

The poster was concluded by stating that future work should be undertaken to determine the associated between SMGs and clinical outcomes.

Reference:
  1. Krysiak K. et al. Recurrent mutations and clinical outcomes in patients with Follicular Lymphoma [Poster]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; 2017. Poster nr [2444 / 1].