MyC, YAP1, and MMP13 gene amplification drive brain metastasis in lung cancer

Brain metastasis occurs in 30%-50% of lung cancer, and brain metastases lung from adenocarcinoma, BM-LUAD) is an important cause of death.
the evolution of BM-LUAD is a complex multi-step process.
molecular genetic changes are the drivers of primary lung adenocarcinoma, it is not clear whether specific molecular changes can lead to BM-LUAD.
recently published genomics analysis shows that there are general molecular genetic differences between primary tumors and metastatic tumor samples, which cause tumor progression to mutate and increase the rate of brain metastasis.
J. H. Shih of the Dana-Farber Cancer Institute in Boston, USA, and others compared BM-LUAD with the primary LUAD to identify genomic changes in brain metastasis, the results of which were published online March 2020 in Nat Genet.
study method The authors analyzed the full exosomal protosequencing (WES) sample from the BM-LUAD group in 73 patients and analyzed the TCGA-LUAD control group with 503 primary LUAD patients in the Cancer Genome Map (TCGA) database.
First, MutSig2CV and dNdScv were used to calculate changes in single nucleotide variation (SNVs) during brain transfer, and then to evaluate changes in the number of copies of genes (SCNA).
test results from 105 BM-LUAD patient data (independent verification group) and LUAD xenotrogen transplant (PDX) mouse models received at the Medical University of Vienna from 1990 to 2013 were used to verify the role of MYC, YAP1 and MMP13 gene amplification in brain metastasis.
results compared the TCGA-LUAD control group with the BM-LUAD group and found that the BM-LUAD increased significantly in the amplification frequency of three regional points compared to 464 TCGA-LUAD matching groups, including MYC (12%:12%: 6%), YAP1 (7%: 0.8%) and MMP13 (10%: 0.6%), and CDKN2A/B have a higher percentage of absences (27%: 13%) (Figure 1).
the increased amplification frequency of MYC, YAP1, and MMP13 in 105 separate BM-LUAD validation groups (Figure 2).
in LUAD heterogenetic transplant mouse models, it was also confirmed that MYC, YAP1, or MMP13 over-expression increased brain metastasis.
Figure 1. The BM-LUAD group was compared with the TCGA-LUAD matching group genome sequencing.
Figure 2. BM-LUAD verification group MYC and YAP1 amplification frequencies.
conclusions The authors conclude that MYC, YAP1, and MMP13 amplification may contribute to brain metastasis in lung cancer, which is a potential therapeutic target for future brain transfer.
to obtain enough brain metastasis tumor samples for genome sequencing, is a feasible method for preventing brain metastasis in lung cancer.
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