TY - JOUR
T1 - Germline predisposition and copy number alteration in pre-stage lung adenocarcinomas presenting as ground-glass nodules
AU - Ren, Yijiu
AU - Huang, Shujun
AU - Dai, Chenyang
AU - Xie, Dong
AU - Zheng, Larry
AU - Xie, Huikang
AU - Zheng, Hui
AU - She, Yunlang
AU - Zhou, Fangyu
AU - Wang, Yue
AU - Li, Pengpeng
AU - Fei, Ke
AU - Jiang, Gening
AU - Zhang, Yang
AU - Su, Bo
AU - Alejandro Sweet-Cordero, E.
AU - Tran, Nhan Le
AU - Yang, Yanan
AU - Patel, Jai N.
AU - Rolfo, Christian
AU - Rocco, Gaetano
AU - Cardona, Andrés Felipe
AU - Tuzi, Alessandro
AU - Suter, Matteo B.
AU - Yang, Ping
AU - Xu, Wayne
AU - Chen, Chang
N1 - Publisher Copyright:
© 2007-2019 Frontiers Media S.A. All Rights Reserved.
PY - 2019
Y1 - 2019
N2 - Objective: Synchronous multiple ground-glass nodules (SM-GGNs) are a distinct entity of lung cancer which has been emerging increasingly in recent years in China. The oncogenesis molecular mechanisms of SM-GGNs remain elusive. Methods: We investigated single nucleotide variations (SNV), insertions and deletions (INDEL), somatic copy number variations (CNV), and germline mutations of 69 SM-GGN samples collected from 31 patients, using target sequencing (TRS) and whole exome sequencing (WES). Results: In the entire cohort, many known driver mutations were found, including EGFR (21.7%), BRAF (14.5%), and KRAS (6%). However, only one out of the 31 patients had the same somatic missense or truncated events within SM-GGNs, indicating the independent origins for almost all of these SM-GGNs. Many germline mutations with a low frequency in the Chinese population, and genes harboring both germline and somatic variations, were discovered in these pre-stage GGNs. These GGNs also bore large segments of copy number gains and/or losses. The CNV segment number tended to be positively correlated with the germline mutations (r = 0.57). The CNV sizes were correlated with the somatic mutations (r = 0.55). A moderate correlation (r = 0.54) was also shown between the somatic and germline mutations. Conclusion: Our data suggests that the precancerous unstable CNVs with potentially predisposing genetic backgrounds may foster the onset of driver mutations and the development of independent SM-GGNs during the local stimulation of mutagens.
AB - Objective: Synchronous multiple ground-glass nodules (SM-GGNs) are a distinct entity of lung cancer which has been emerging increasingly in recent years in China. The oncogenesis molecular mechanisms of SM-GGNs remain elusive. Methods: We investigated single nucleotide variations (SNV), insertions and deletions (INDEL), somatic copy number variations (CNV), and germline mutations of 69 SM-GGN samples collected from 31 patients, using target sequencing (TRS) and whole exome sequencing (WES). Results: In the entire cohort, many known driver mutations were found, including EGFR (21.7%), BRAF (14.5%), and KRAS (6%). However, only one out of the 31 patients had the same somatic missense or truncated events within SM-GGNs, indicating the independent origins for almost all of these SM-GGNs. Many germline mutations with a low frequency in the Chinese population, and genes harboring both germline and somatic variations, were discovered in these pre-stage GGNs. These GGNs also bore large segments of copy number gains and/or losses. The CNV segment number tended to be positively correlated with the germline mutations (r = 0.57). The CNV sizes were correlated with the somatic mutations (r = 0.55). A moderate correlation (r = 0.54) was also shown between the somatic and germline mutations. Conclusion: Our data suggests that the precancerous unstable CNVs with potentially predisposing genetic backgrounds may foster the onset of driver mutations and the development of independent SM-GGNs during the local stimulation of mutagens.
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U2 - 10.3389/fonc.2019.00288
DO - 10.3389/fonc.2019.00288
M3 - Article
AN - SCOPUS:85066735130
SN - 2234-943X
VL - 9
JO - Frontiers in Oncology
JF - Frontiers in Oncology
IS - MAR
M1 - 288
ER -