Abstract
Novel LTK fusions based on NGS sequencing data in Chinese patients with solid tumors.
Author
person
Hui Chen
Shanghai OrigiMed Co., Ltd, Shanghai, China
info_outline
Hui Chen, Shaohua Yuan, Xiaoliang Shi, Fei Pang
Full text
Authors
person
Hui Chen
Shanghai OrigiMed Co., Ltd, Shanghai, China
info_outline
Hui Chen, Shaohua Yuan, Xiaoliang Shi, Fei Pang
Organizations
Shanghai OrigiMed Co., Ltd, Shanghai, China, Shanghai OrigiMed Co., Ltd., Shanghai, China
Abstract Disclosures
Research Funding
No funding received
None.
Background:
Leukocyte receptor tyrosine kinase (
LTK)
gene has the same kinase domain (PTKc_ALK_LTK) as
ALK
, and could functionally response to ALK inhibitors such as lorlatinib. Previous study reported that
CLIP1-LTK
fusion was a novel oncogenic driver mutation in lung cancer (occur in 0.4% of non-small cell lung cancer), which was sensitive to the ALK tyrosine kinase inhibitor lorlatinib. So far,
LTK
fusion has been rarely reported.
Methods:
A total of 11 Chinese solid tumor patients were reviewed, including 6 cases of
LTK
positive rearrangements in DNA and 5 cases of
LTK
positive fusion in RNA. FFPE samples were collected for NGS-based 450 cancer gene panel detection in both DNA and RNA level, and matched blood samples were used as normal control to filter out germline mutations.
LTK
fusions were analyzed by OrigiFus algorithm.
Results:
We found 6 patients with
LTK
rearrangements by DNA-based NGS detection, including lung adenocarcinoma, colorectal cancer, stomach cancer, spindle cell sarcoma of small intestine, adenocarcinoma of the pancreas, and cancer of unknown primary, and 5 soft tissue sarcoma patients with
RPAP1
E25-
LTK
E2 fusions by RNA-based NGS detection. We analyzed the patterns of partner genes and breakpoints of the 6
LTK
rearrangements. The partner genes included
NUSAP1
(n=2),
NDUFAF1
(n=1),
LOC105370802
(n=1),
EHD4
(n=1), and
AGBL1
(n=1). All these partner genes were located on the same chromosome as
LTK
, rather than
CLIP1,
which was identified as a translocation. The breakpoints on
LTK
included exon20 (n=2), intron1 (n=2), exon6 (n=1), and exon10 (n=1). Five of the 6 fusions consisted of a complete PTKc_ALK_LTK domain. Among the 6
LTK
rearrangements,
LTK
E20-
NUSAP1
E2 was predicted as a fusion. Interestingly, this clinical real-world sample also harbored a classic
NTRK1
fusion,
LMNA
E2-
NTRK1
E11. The other
NUSAP1
-
LTK
was predicted to have a transcript of 3’-3’, but one of the breakpoints was observed at
LTK
exon6, which could be located at the kinase domain, so the possibility of eventual fusion cannot be excluded. The two
NUSAP1-LTK
fusions were found in a stomach tumor and a soft tissue sarcoma, respectively. One non-small-cell lung cancer (NSCLC) patient had a breakpoint detected on
LTK
exon10, which is the same as the exon of
CLIP1
-
LTK
reported.
Conclusions:
This study revealed novel
LTK
fusions/rearrangements and their cancer distribution in Chinese patients with solid tumors. We gave the details of these fusions/rearrangements which enrich our understanding of the
LTK
fusion. Although the small number of cases, our analysis promoted the attention on
LTK
and its potential value of drug research and clinical treatment in pan-cancer.
1 organization
1 drug
1 target
Organization
Shanghai OrigiMed Co., Ltd., Shanghai, ChinaDrug
lorlatinibTarget
LTK