PMID- 26754874
OWN - NLM
STAT- MEDLINE
DCOM- 20170117
LR  - 20181113
IS  - 2212-4934 (Electronic)
IS  - 2212-4926 (Print)
IS  - 2212-4926 (Linking)
VI  - 60
DP  - 2016 Jan
TI  - The chromosome 3q26 OncCassette: A multigenic driver of human cancer.
PG  - 47-63
LID - S2212-4926(15)30037-3 [pii]
LID - 10.1016/j.jbior.2015.10.009 [doi]
AB  - Recurrent copy number variations (CNVs) are genetic alterations commonly observed 
      in human tumors. One of the most frequent CNVs in human tumors involves copy 
      number gains (CNGs) at chromosome 3q26, which is estimated to occur in >20% of 
      human tumors. The high prevalence and frequent occurrence of 3q26 CNG suggest 
      that it drives the biology of tumors harboring this genetic alteration. The 
      chromosomal region subject to CNG (the 3q26 amplicon) spans from chromosome 3q26 
      to q29, a region containing  approximately 200 protein-encoding genes. The large number of 
      genes within the amplicon makes it difficult to identify relevant oncogenic 
      target(s). Whereas a number of genes in this region have been linked to the 
      transformed phenotype, recent studies indicate a high level of cooperativity 
      among a subset of frequently amplified 3q26 genes. Here we use a novel 
      bioinformatics approach to identify potential driver genes within the recurrent 
      3q26 amplicon in lung squamous cell carcinoma (LSCC). Our analysis reveals a set 
      of 35 3q26 amplicon genes that are coordinately amplified and overexpressed in 
      human LSCC tumors, and that also map to a major LSCC susceptibility locus 
      identified on mouse chromosome 3 that is syntenic with human chromosome 3q26. 
      Pathway analysis reveals that 21 of these genes exist within a single predicted 
      network module. Four 3q26 genes, SOX2, ECT2, PRKCI and PI3KCA occupy the hub of 
      this network module and serve as nodal genes around which the network is 
      organized. Integration of available genetic, genomic, biochemical and functional 
      data demonstrates that SOX2, ECT2, PRKCI and PIK3CA are cooperating oncogenes 
      that function within an integrated cell signaling network that drives a highly 
      aggressive, stem-like phenotype in LSCC tumors harboring 3q26 amplification. 
      Based on the high level of genomic, genetic, biochemical and functional 
      integration amongst these 4 3q26 nodal genes, we propose that they are the key 
      oncogenic targets of the 3q26 amplicon and together define a "3q26 OncCassette" 
      that mediates 3q26 CNG-driven tumorigenesis. Genomic analysis indicates that the 
      3q26 OncCassette also operates in other major tumor types that exhibit frequent 
      3q26 CNGs, including head and neck squamous cell carcinoma (HNSCC), ovarian 
      serous cancer and cervical cancer. Finally, we discuss how the 3q26 OncCassette 
      represents a tractable target for development of novel therapeutic intervention 
      strategies that hold promise for improving treatment of 3q26-driven cancers.
CI  - Copyright (c) 2015 Elsevier Ltd. All rights reserved.
FAU - Fields, Alan P
AU  - Fields AP
AD  - Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, 
      Jacksonville, FL, United States. Electronic address: fields.alan@mayo.edu.
FAU - Justilien, Verline
AU  - Justilien V
AD  - Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, 
      Jacksonville, FL, United States.
FAU - Murray, Nicole R
AU  - Murray NR
AD  - Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, 
      Jacksonville, FL, United States.
LA  - eng
GR  - R01 CA14090-05/CA/NCI NIH HHS/United States
GR  - R01 CA081436/CA/NCI NIH HHS/United States
GR  - R21 CA151250-02/CA/NCI NIH HHS/United States
GR  - R21 CA153000/CA/NCI NIH HHS/United States
GR  - R21 CA151250/CA/NCI NIH HHS/United States
GR  - R01 CA081436-16/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20151223
PL  - England
TA  - Adv Biol Regul
JT  - Advances in biological regulation
JID - 101572336
SB  - IM
MH  - Animals
MH  - Chromosomes, Human, Pair 3/*genetics/metabolism
MH  - DNA Copy Number Variations
MH  - Gene Amplification
MH  - Humans
MH  - Mice
MH  - Neoplasms/*genetics/metabolism
MH  - Oncogenes
PMC - PMC4729592
MID - NIHMS747182
OTO - NOTNLM
OT  - 3q26 amplicon
OT  - Amplification
OT  - Cancer
OT  - Copy number gain (CNG)
OT  - OncCassette
OT  - Oncogenic drivers
COIS- Conflicts of Interest: None to declare
EDAT- 2016/01/13 06:00
MHDA- 2017/01/18 06:00
PMCR- 2017/01/01
CRDT- 2016/01/13 06:00
PHST- 2015/10/26 00:00 [received]
PHST- 2015/10/28 00:00 [revised]
PHST- 2015/10/29 00:00 [accepted]
PHST- 2016/01/13 06:00 [entrez]
PHST- 2016/01/13 06:00 [pubmed]
PHST- 2017/01/18 06:00 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - S2212-4926(15)30037-3 [pii]
AID - 10.1016/j.jbior.2015.10.009 [doi]
PST - ppublish
SO  - Adv Biol Regul. 2016 Jan;60:47-63. doi: 10.1016/j.jbior.2015.10.009. Epub 2015 
      Dec 23.