Abstract | BACKGROUND: METHODS: Fine needle biopsies were taken from the primary tumor (PT) and a secondary bone metastasis (BM) of 17 LABM patients before treatment. Simple genetic profiles for selecting therapies were initially obtained using an ARMS-PCR test for EGFR and ALK fusion mutations. More detailed genetic profiles of somatic exon SNVs and CNVs in 457 cancer-related genes were retrospectively derived using capture single molecule amplification and resequencing technology (capSMART). RESULTS: ARMS-PCR identified 14 EGFR positive, 3 EGFR negative and 1 ALK fusion positive patient. A therapy regimen incorporating TKIs Gefitinib and Crizotinib was offered to the EGFR and ALK fusion positive patients, respectively. With the exception of two patients, molecular profiling of matching PT and BM biopsies identified a highly shared somatic variant fingerprint, although the BMs exhibited additional genomic instability. In six of 13 EGFR positive patients and in all three EGFR negative patients, examination of the genetic profiles identified additional clinically significant mutations that are known or experimental drug targets for treatment of lung cancer. CONCLUSION: Our findings firstly suggest that treatment regimens based on comprehensive genetic assessment of newly diagnosed LABM patients should target both the PT and secondary BMs, including rogue clones with potential to form new BMs. Second, the additional information gained should allow clinicians to design and implement more personalized treatment regimens and potentially improve outcomes for LABM patients.
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Authors | Long Huang, Xiao-Liu Jiang, Hong-Bin Liang, Jian-Cheng Li, Li-Han Chin, Jian-Ping Wei, Rui-Ru Wang, Jing Cai, Qiang Xiong, Lien-Tu Wang, David S Cram, An-Wen Liu |
Journal | Molecular medicine (Cambridge, Mass.)
(Mol Med)
Vol. 26
Issue 1
Pg. 88
(09 17 2020)
ISSN: 1528-3658 [Electronic] England |
PMID | 32942985
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
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Topics |
- Adenocarcinoma of Lung
(genetics, pathology)
- Aged
- Biomarkers, Tumor
- Biopsy
- Bone Neoplasms
(diagnosis, drug therapy, secondary)
- Female
- Gene Expression Profiling
(methods)
- Humans
- Male
- Middle Aged
- Molecular Targeted Therapy
- Mutation
- Neoplasm Grading
- Neoplasm Staging
- Neoplasms, Second Primary
(diagnosis, drug therapy, etiology)
- Transcriptome
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