SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas.
Lineage-survival oncogenes are activated by somatic DNA alterations in cancers arising from the cell lineages in which these genes play a role in normal development. Here we show that a peak of genomic amplification on chromosome 3q26.33 found in squamous cell carcinomas (SCCs) of the lung and esophagus contains the transcription factor gene SOX2, which is mutated in hereditary human esophageal malformations, is necessary for normal esophageal squamous development, promotes differentiation and proliferation of basal tracheal cells and cooperates in induction of pluripotent stem cells. SOX2 expression is required for proliferation and anchorage-independent growth of lung and esophageal cell lines, as shown by RNA interference experiments. Furthermore, ectopic expression of SOX2 here cooperated with FOXE1 or FGFR2 to transform immortalized tracheobronchial epithelial cells. SOX2-driven tumors show expression of markers of both squamous differentiation and pluripotency. These characteristics identify SOX2 as a lineage-survival oncogene in lung and esophageal SCC.
Adam J
AJ
Bass
Hideo
H
Watanabe
Craig H
CH
Mermel
Soyoung
S
Yu
Sven
S
Perner
Roel G
RG
Verhaak
So Young
SY
Kim
Leslie
L
Wardwell
Pablo
P
Tamayo
Irit
I
Gat-Viks
Alex H
AH
Ramos
Michele S
MS
Woo
Barbara A
BA
Weir
Gad
G
Getz
Rameen
R
Beroukhim
Michael
M
O'Kelly
Amit
A
Dutt
Orit
O
Rozenblatt-Rosen
Piotr
P
Dziunycz
Justin
J
Komisarof
Lucian R
LR
Chirieac
Christopher J
CJ
Lafargue
Veit
V
Scheble
Theresia
T
Wilbertz
Changqing
C
Ma
Shilpa
S
Rao
Hiroshi
H
Nakagawa
Douglas B
DB
Stairs
Lin
L
Lin
Thomas J
TJ
Giordano
Patrick
P
Wagner
John D
JD
Minna
Adi F
AF
Gazdar
Chang Qi
CQ
Zhu
Marcia S
MS
Brose
Ivan
I
Cecconello
Ulysses
U
Ribeiro
Suely K
SK
Marie
Olav
O
Dahl
Ramesh A
RA
Shivdasani
Ming-Sound
MS
Tsao
Mark A
MA
Rubin
Kwok K
KK
Wong
Aviv
A
Regev
William C
WC
Hahn
David G
DG
Beer
Anil K
AK
Rustgi
Matthew
M
Meyerson
D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D002454:Cell Differentiation; D019070:Cell Lineage; D002470:Cell Survival; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D005784:Gene Amplification; D015894:Genome, Human; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D009857:Oncogenes / Q000235:genetics*; D034622:RNA Interference; D055748:SOXB1 Transcription Factors / Q000235:genetics*
C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors