Molecular Evolution Patterns in Metastatic Lymph Nodes Reflect the Differential Treatment Response of Advanced Primary Lung Cancer

被引：15

作者：

Um, Sang-Won ^{[1
]}

Joung, Je-Gun ^{[2
]}

Lee, Hyun ^{[1
]}

Kim, Hojoong ^{[1
]}

Kim, Kyu-Tae ^{[2
]}

Park, Jinha ^{[1
]}

Hayes, D. Neil ^{[3
]}

Park, Woong-Yang ^{[2
,4
]}

机构：

[1] Sungkyunkwan Univ, Div Pulm & Crit Care Med, Samsung Med Ctr, Dept Med,Sch Med, Seoul, South Korea

[2] Samsung Med Ctr, Samsung Genome Inst, 81 Irwon Ro, Seoul 06351, South Korea

[3] Univ North Carolina Chapel Hill, Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA

[4] Sungkyunkwan Univ, Dept Mol Cell Biol, Sch Med, Seoul, South Korea

来源：

CANCER RESEARCH | 2016年 / 76卷 / 22期

关键词：

EML4-ALK FUSION GENE; INTRATUMOR HETEROGENEITY; SIGNALING PATHWAY; KINASE INHIBITOR; MUTATIONS; EGFR; CHEMOTHERAPY; RESISTANCE; DRIVERS; GROWTH;

D O I：

10.1158/0008-5472.CAN-16-0873

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Tumor heterogeneity influences the clinical outcome of patients with cancer, and the diagnostic method to measure the tumor heterogeneity needs to be developed. We analyzed genomic features on pairs of primary and multiple metastatic lymph nodes from six patients with lung cancer using whole-exome sequencing and RNA sequencing. Although somatic single-nucleotide variants were shared in primary lung cancer and metastases, tumor evolution predicted by the pattern of genomic alterations was matched to anatomic location of the tumors. Four of six cases exhibited a branched clonal evolution pattern. Lymph nodes with acquired somatic variants demonstrated resistance to the cancer treatment. In this study, we demonstrated that multiple biopsies and sequencing strategies for different tumor regions are required for a comprehensive understanding of the landscape of genetic alteration and for guiding targeted therapy in advanced primary lung cancer. (C) 2016 AACR.

引用

页码：6568 / 6576

页数：9

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