NOTCH1 mutations in CLL associated with trisomy 12
Menée sur des échantillons tumoraux prélevés sur 186 patients atteints d'une leucémie lymphocytaire chronique, cette étude identifie de fréquentes mutations du gène NOTCH1 en association avec une trisomie 12
Two recent studies reported whole genome sequencing of CLL samples and found repeated mutations in the XPO1 and NOTCH1 genes. XPO1 was found mutated in 2.4% cases, while NOTCH1 was found mutated in 12.2% or 15.1% of CLL samples. Here we report the results of sequencing of XPO1 and NOTCH1 in 186 CLL cases. Our results confirmed frequency of XPO1 mutations. However, we found only 5 NOTCH1 mutations in 127 IGVH unmutated/ZAP-70+ CLL samples (4%), and one mutation were found in IGVH mutated/ZAP-70- CLL for a total percentage of 1.5%. Since 4 of 6 mutated samples also showed trisomy 12, we sequenced NOTCH1 in additional 77 cases with trisomy 12 CLLs, including 47 IGVH unmutated/ZAP-70+ cases. Importantly, we found 41.9% NOTCH1 mutation frequency in aggressive trisomy 12 CLL cases. Our data suggest that activation of NOTCH1 plays a critical role in IGVH unmutated/ZAP-70+ trisomy 12 CLL.