Molecular characterization of cancers with ALK gene fusions in nonlung tumors.

Authors

null

Jin Zhang

Department of Thoracic Surgery,China-Japan Friendship Hospital, Beinjing, China

Jin Zhang , Yushuai Han , Weiran Wang , Mengxiang Xu , Jianhua Zhu , Tonghui Ma

Organizations

Department of Thoracic Surgery,China-Japan Friendship Hospital, Beinjing, China, Genetron Health (Beijing) Technology, Beijing, China, Genetron Health (Hangzhou) Medical Laboratory Co. Ltd., Hangzhou, China, Genetron Health (Beijing) Technology, Co. Ltd, Beijing, China, Genetron Health (Beijing) Technology, Co. Ltd., Beijing, China

Research Funding

No funding received

Background: ALK gene rearrangement is known as “diamond mutation”. Targeted tyrosine kinase inhibitors have perfect therapeutic effects on ALK fusion lung cancer patients (pts), but the molecular characteristics of ALK fusions in other cancers have not been systematically elucidated. Methods: We retrospectively analyzed the NGS data of ALK fusion-positive Chinese tumor pts (n = 1068) to characterize ALK fusions in pan-cancer (excluding lung cancer) pts. Results: A total of 66 ALK fusion-positive pts with 13 types of cancer (excluding lung cancer) were screened, including 0.4% (24/5800) of brain tumor pts, 0.1% (11/7725) of gastrointestinal cancer pts, 0.4% (7/1741) of thyroid cancer pts, 0.5% (8/1732) of sarcoma pts, 0.2% (4/2031) of liver cancer pts, 0.6% (3/540) of melanoma pts, 9% (2/22) of inflammatory myofibroblastic tumor pts, 2.5% (2/79) of embryonal tumor pts, 0.4% (1/282) of lymphoma pts, 3.2% (1/31) of parotid carcinoma pts, 0.1% (1/985) of breast cancer pts, 0.4% (1/241) of prostatic cancer pts and 0.3% (1/320) of ovarian cancer pts. Herein, we reported 28 ALK fusion patterns, of which the most common partners were EML4 (n = 24) and STRN (n = 8), and mainly occurred in brain tumors (14/24, 58.8%) and thyroid cancers (6/8, 75%), respectively. In addition, there were 8 ALK fusion modes that were never reported before. Of the ALK fusion patterns described above, 92.4% (61/66) of fusions were located at the most canonical site of ALK (exon20), preserving the intact kinase domain. Meanwhile, rare fusion positions in the ALK gene were also found, such as PPP1CB-ALK(ex2:ex4), NUP107-ALK(ex20:ex3), COL14A1-ALK(ex8:ex4), BRAF-ALK(ex9:ex4), which preserve the extracellular and transmembrane domains, as well as RASD2-ALK(ex2:ex24), of which the breakpoint in ALK gene may disrupt the formation of kinase domain. Conclusions: We demonstrated the rarity of ALK gene fusions in nonlung cancers. Analyzing the ALK fusion characteristics of these cancer may help to clarify their pathogenesis and provide ideas for new drug treatment.

Partners of ALK gene fusions.

Partners
Counts
Partners
Counts
Partners
Counts
Partners
Counts
Known fusions
EML4
24
KIF5B
2
FN1
1
TIMP3
1
STRN
8
PPP1CB
2
KLC1
1
TPM3
1
DCTN1
3
TPM4
2
PLEKHH2
1
LCLAT1
1
NPM1
3
CLIP2
1
PRKAR2A
1
PABPC1
1
ATIC
2
CLTC
1
RANBP2
1
HMBOX1
1
Unreported fusions
AMN
1
GTF2I
1
RASD2
1
BRAF
1
NUP107
1
TBC1D16
1
COL14A1
1
ZKSCAN1
1

Disclaimer

This material on this page is ©2024 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact licensing@asco.org

Abstract Details

Meeting

2022 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

Track

Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

Sub Track

Tissue-Based Biomarkers

Citation

J Clin Oncol 40, 2022 (suppl 16; abstr 3121)

DOI

10.1200/JCO.2022.40.16_suppl.3121

Abstract #

3121

Poster Bd #

113

Abstract Disclosures

Similar Abstracts

Abstract

2022 ASCO Annual Meeting

ALK fusion typing and response to crizotinib in ALK+ lung cancer-naive patients.

First Author: Xinliang Zhou

Abstract

2022 ASCO Annual Meeting

Driver coexistence characteristics of ALK-fusion in Chinese patients with lung cancer.

First Author: Min Gao