Circulating tumor DNA analysis depicts subclonal architecture and genomic evolution of small cell lung cancer.
Jingying NongYuhua GongYanfang GuanXin YiYuting YiLianpeng ChangLing YangJialin LvZhirong GuoHongyan JiaYuxing ChuTao LiuMing ChenLauren ByersEmily RoartyVincent K LamVassiliki A PapadimitrakopoulouIgnacio WistubaJohn V HeymachBonnie GlissonZhongxing LiaoJiun-Kae Jack LeeP Andrew FutrealShucai ZhangXuefeng XiaJianjun ZhangJinghui WangPublished in: Nature communications (2018)
Subclonal architecture and genomic evolution of small-cell lung cancer (SCLC) under treatment has not been well studied primarily due to lack of tumor specimens, particularly longitudinal samples acquired during treatment. SCLC is characterized by early hematogenous spread, which makes circulating cell-free tumor DNA (ctDNA) sequencing a promising modality for genomic profiling. Here, we perform targeted deep sequencing of 430 cancer genes on pre-treatment tumor biopsies, as well as on plasma samples collected prior to and during treatment from 22 SCLC patients. Similar subclonal architecture is observed between pre-treatment ctDNA and paired tumor DNA. Mean variant allele frequency of clonal mutations from pre-treatment ctDNA is associated with progression-free survival and overall survival. Pre- and post-treatment ctDNA mutational analysis demonstrate that mutations of DNA repair and NOTCH signaling pathways are enriched in post-treatment samples. These data suggest that ctDNA sequencing is promising to delineate genomic landscape, subclonal architecture, and genomic evolution of SCLC.
Keyphrases
- circulating tumor
- cell free
- small cell lung cancer
- dna repair
- single cell
- free survival
- chronic kidney disease
- signaling pathway
- young adults
- newly diagnosed
- end stage renal disease
- combination therapy
- transcription factor
- drug delivery
- cell proliferation
- ejection fraction
- genome wide
- lymph node metastasis
- cancer therapy
- endoplasmic reticulum stress
- prognostic factors
- dna damage response
- ultrasound guided
- artificial intelligence