Coexisting of COX7A2L-ALK, LINC01210-ALK, ATP13A4-ALK and Acquired SLCO2A1-ALK in a Lung Adenocarcinoma with Rearrangements Loss During the Treatment of Crizotinib and Ceritinib: A Case Report.

Abstract:

:ALK rearrangements account for ~5% of non-small-cell lung cancer (NSCLC). Numerous rearrangement partners have been discovered. Here, we describe a 53-year-old nonsmoker with NSCLC, in whom we identified four novel rearrangements. The patient was diagnosed as adenocarcinoma in the right middle lobe of lung, with metastases in subcarinal lymph node, ipsilateral lung, pleura and contralateral rib (cT4N2M1, stage IV). Next-generation sequencing (NGS) identified three baseline ALK fusions: COX7A2L-ALK (C[intragenic]:A20), LINC01210-ALK (L[intergenic]:A20) and ATP13A4-ALK (A9:A19). The patient exhibited 12 months of progression-free survival (PFS) and a partial response (PR) to first-line crizotinib therapy. We then discovered a new SLCO2A1-ALK fusion (S[intergenic]:A18) and a missense mutation C1156Y after resistance developed. Sequential ceritinib resulted in further 8 months of PFS, after which NGS results demonstrated the loss of ATP13A4-ALK and SLCO2A1-ALK. This is the first description a NSCLC patient harbors four ALK fusions and was sensitive to tyrosine kinase inhibitors (TKIs). Acquisition and loss of ALK fusions after ALK inhibitors may account for resistance.

journal_name

Onco Targets Ther

journal_title

OncoTargets and therapy

authors

Cai C,Long Y,Li Y,Huang M

doi

10.2147/OTT.S258067

subject

Has Abstract

pub_date

2020-08-20 00:00:00

pages

8313-8316

issn

1178-6930

pii

258067

journal_volume

13

pub_type

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    pub_type:

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    doi:10.2147/OTT.S99166

    authors: Cheng W,Feng F,Ma C,Wang H

    更新日期:2016-03-11 00:00:00

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    journal_title:OncoTargets and therapy

    pub_type:

    doi:10.2147/OTT.S223568

    authors: Lin J,Yang X,Xie Y,Zhao H

    更新日期:2019-11-19 00:00:00

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    doi:10.2147/ott.s3027

    authors: Lukas RV,Boire A,Nicholas MK

    更新日期:2009-02-18 00:00:00