Abstract 102P
Background
Constitute activation of JAK signaling pathway is associated with the pathogenesis of multiple hematological tumors such as myelofibrosis, which can be targeted by JAK inhibitors, Ruxolitinib and Fedratinib. Similar to hematological tumors, JAK signaling pathway is frequently mutated in many solid tumors, these patients (pts) may also benefit from JAK inhibitors. However, there is little systematic analysis of JAK family genes in solid tumors. In this present study, we described and analyzed the genomic alterations of JAK family in Chinese pan-cancer pts.
Methods
11159 Chinese cancer pts spanning various solid tumors, including lung cancer, liver cancer, intestine cancer, bile duct cancer, brain cancer, gastric cancer, etc., were analyzed by high-throughput sequencing technology.
Results
The mutation frequency of JAK1 and JAK2 in Chinese solid tumor pts was 1.08% (121/11159) and 2.12% (237/11159), respectively. The most common mutations in JAK1 were S729C (9.92%, 12/121), K860Nfs*16 (7.30%, 10/121) and S703I (7.44%, 9/121). JAK3 gene mutation rate was 1.63% (182/11159) in solid tumors, including A746V (2.20%, 4/182), Q743L (2.20%, 4/182), and Q39Sfs*108 (2.20%, 4/182). Interestingly, consistent with hematological tumors, V617F was also the most frequent mutation type of JAK2 gene in solid tumors, and other hotspot mutations included G127D (14.77%, 35/237) and E66K (2.11%, 5/237). Gain-of-function mutations of JAK genes were potential targets of JAK inhibitors. Across all tumor types, the proportion of pts with JAK activating mutations was 0.49% (55/11159). Liver cancer accounted for the highest proportion of activating mutations (1.76%, 22/1252), followed by Lung cancer (0.50%, 25/5022) and Intestinal cancer (0.19%, 3/1586). In lung cancer, 80% of the JAK activating mutations occurred in JAK2, while only gain-of-function mutations happened in JAK1 could be detected in liver cancer pts.
Conclusions
Our research depicts the panoramic features of JAK family gene mutations in Chinese cancer patients, which will be helpful in expanding our understanding of JAK family genes in solid tumors.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.