HIP1–ALK, A Novel ALK Fusion Variant that Responds to Crizotinib

Abstract

Discovery of HIP1 as a fusion partner of ALK in NSCLC is a novel finding. In addition, the HIP1-ALK-rearranged tumor is sensitive to treatment with crizotinib in vivo, implicating HIP1-ALKas an oncogenic driver of lung tumorigenesis. Collectively, our results indicate that HIP1-ALK-positive NSCLC may benefit from clinical applications of crizotinib.

ALK, ROS1 and RET rearrangements in lung squamous cell carcinoma are very rare

“…However, tumors with squamous cell carcinoma or adenosquamous histologies, albeit at a lower frequency (∼1%) than adenocarcinomas, have been reported to carry ALK translocations [6,26,28,32,35,[40][41][42][43]. Based on the NanoString fusion panel, we have examined a total of 282 cases of lung SCC combining the 214 from this study and the 68 from the published results of Fang et al [32]. Our combined data revealed that ALK rearrangement occurred in 0.7% of lung squamous cell carcinoma in Asian populations with resected lung cancer.…”

“…Using NanoString fusion panel, Fang et al identified two ALKrearranged SCC xenograft models, one carrying the well-known EML4-ALK variants 3a/b and the other harboring a novel huntingtin interacting protein 1 (HIP1)-ALK fusion gene [32]. Both were diagnosed as moderately differentiated SCC by a pathologist, and then further validated by an immunohistochemistry panel positive for CK5/6, p63, 34␤E12 and negative for MOC31 and BerEP4.…”

Anaplastic lymphoma kinase rearrangement in lung Cancer: Its biological and clinical significance

“…Preclinical data reported by Heuchman et al showed that variant 2 is more sensitive to ALK inhibitors than variants 1 and 3a/b, which was considered to be due to the differential protein stability among the variants; however, it remains unclear whether the type of variant can predict the response to treatment with ALK inhibitors in ALK-rearranged patients [12,31]. Other partners, such as the kinesin family member 5B (KIF5B), TRK-fused gene (TFG) and huntingtin interacting protein 1 (HIP1) genes, have also been identified to fuse with the ALK gene in patients with lung cancer, thus resulting in oncogenic transformation [32][33][34].…”

Standard immunohistochemistry efficiently screens for anaplastic lymphoma kinase rearrangements in differentiated thyroid cancer

“…, where E 3 is the geometric mean of ALK 3 0 probe expression, A 5 is the average of ALK 5 0 probe expression, and B is the background threshold as defined previously (Lira et al 2013, Fang et al 2014. The thresholds for RET and fusion probes were calculated in a similar manner as described previously (Lira et al 2013, Fang et al 2014.…”

“…The thresholds for RET and fusion probes were calculated in a similar manner as described previously (Lira et al 2013, Fang et al 2014.…”