PMID- 31968252
OWN - NLM
STAT- MEDLINE
DCOM- 20210317
LR  - 20231103
IS  - 2211-1247 (Electronic)
VI  - 30
IP  - 3
DP  - 2020 Jan 21
TI  - Chromosome 3q26 Gain Is an Early Event Driving Coordinated Overexpression of the 
      PRKCI, SOX2, and ECT2 Oncogenes in Lung Squamous Cell Carcinoma.
PG  - 771-782.e6
LID - S2211-1247(19)31728-0 [pii]
LID - 10.1016/j.celrep.2019.12.071 [doi]
AB  - Lung squamous cell carcinoma (LSCC) is a prevalent form of lung cancer exhibiting 
      distinctive histological and genetic characteristics. Chromosome 3q26 copy number 
      gain (CNG) is a genetic hallmark of LSCC present in >90% of tumors. We report 
      that 3q26 CNGs occur early in LSCC tumorigenesis, persist during tumor 
      progression, and drive coordinate overexpression of PRKCI, SOX2, and ECT2. 
      Overexpression of PRKCI, SOX2, and ECT2 in the context of Trp53 loss is 
      sufficient to transform mouse lung basal stem cells into tumors with histological 
      and genomic features of LSCC. Functionally, PRKCI and SOX2 collaborate to 
      activate an extensive transcriptional program that enforces a lineage-restricted 
      LSCC phenotype, whereas PRKCI and ECT2 collaborate to promote oncogenic growth. 
      Gene signatures indicative of PKCiota-SOX2 and PKCiota-ECT2 signaling activity are 
      enriched in the classical subtype of human LSCC and predict distinct therapeutic 
      vulnerabilities. Thus, the PRKCI, SOX2, and ECT2 oncogenes represent a multigenic 
      driver of LSCC.
CI  - Copyright (c) 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Liu, Yi
AU  - Liu Y
AD  - Department of Cancer Biology, Mayo Clinic Florida, Jacksonville, FL 32224, USA.
FAU - Yin, Ning
AU  - Yin N
AD  - Department of Cancer Biology, Mayo Clinic Florida, Jacksonville, FL 32224, USA.
FAU - Wang, Xue
AU  - Wang X
AD  - Department of Health Sciences Research, Mayo Clinic Florida, Jacksonville, FL 
      32224, USA.
FAU - Khoor, Andras
AU  - Khoor A
AD  - Department of Pathology, Mayo Clinic Florida, Jacksonville, FL 32224, USA.
FAU - Sambandam, Vaishnavi
AU  - Sambandam V
AD  - Department of Cancer Biology, Mayo Clinic Florida, Jacksonville, FL 32224, USA.
FAU - Ghosh, Anwesha B
AU  - Ghosh AB
AD  - Department of Cancer Biology, Mayo Clinic Florida, Jacksonville, FL 32224, USA.
FAU - Fields, Zoe A
AU  - Fields ZA
AD  - Department of Cancer Biology, Mayo Clinic Florida, Jacksonville, FL 32224, USA.
FAU - Murray, Nicole R
AU  - Murray NR
AD  - Department of Cancer Biology, Mayo Clinic Florida, Jacksonville, FL 32224, USA.
FAU - Justilien, Verline
AU  - Justilien V
AD  - Department of Cancer Biology, Mayo Clinic Florida, Jacksonville, FL 32224, USA. 
      Electronic address: justilien.verline@mayo.edu.
FAU - Fields, Alan P
AU  - Fields AP
AD  - Department of Cancer Biology, Mayo Clinic Florida, Jacksonville, FL 32224, USA. 
      Electronic address: fields.alan@mayo.edu.
LA  - eng
GR  - R01 CA081436/CA/NCI NIH HHS/United States
GR  - R01 CA140290/CA/NCI NIH HHS/United States
GR  - R01 CA206367/CA/NCI NIH HHS/United States
GR  - R03 CA235189/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - 0 (ECT2 protein, human)
RN  - 0 (Isoenzymes)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (SOX2 protein, human)
RN  - 0 (SOXB1 Transcription Factors)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.13 (protein kinase C lambda)
SB  - IM
MH  - Carcinogenesis/genetics/pathology
MH  - Carcinoma, Non-Small-Cell Lung/*genetics/pathology
MH  - Carcinoma, Squamous Cell/*genetics/pathology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/genetics
MH  - Cell Transformation, Neoplastic
MH  - Chromosomes, Human, Pair 3/*genetics
MH  - Gene Dosage
MH  - Gene Expression Regulation, Neoplastic
MH  - Gene Silencing
MH  - Humans
MH  - Isoenzymes/*genetics
MH  - Lung Neoplasms/*genetics/pathology
MH  - Male
MH  - *Oncogenes
MH  - Protein Kinase C/*genetics
MH  - Proto-Oncogene Proteins/*genetics
MH  - SOXB1 Transcription Factors/*genetics
MH  - Signal Transduction
MH  - Transcription, Genetic
PMC - PMC7238436
MID - NIHMS1551546
OTO - NOTNLM
OT  - 3q26 copy number gain
OT  - CNG
OT  - ECT2
OT  - LSCC
OT  - PRKCI
OT  - SOX2
OT  - lung basal stem cells
OT  - lung squamous cell carcinoma
OT  - oncogenic transformation
COIS- Declaration of Interests The authors declare no competing interests.
EDAT- 2020/01/23 06:00
MHDA- 2021/03/18 06:00
PMCR- 2020/05/20
CRDT- 2020/01/23 06:00
PHST- 2019/10/24 00:00 [received]
PHST- 2019/11/27 00:00 [revised]
PHST- 2019/12/18 00:00 [accepted]
PHST- 2020/01/23 06:00 [entrez]
PHST- 2020/01/23 06:00 [pubmed]
PHST- 2021/03/18 06:00 [medline]
PHST- 2020/05/20 00:00 [pmc-release]
AID - S2211-1247(19)31728-0 [pii]
AID - 10.1016/j.celrep.2019.12.071 [doi]
PST - ppublish
SO  - Cell Rep. 2020 Jan 21;30(3):771-782.e6. doi: 10.1016/j.celrep.2019.12.071.