PMID- 24341335
OWN - NLM
STAT- MEDLINE
DCOM- 20140623
LR  - 20220408
IS  - 1471-2407 (Electronic)
IS  - 1471-2407 (Linking)
VI  - 13
DP  - 2013 Dec 17
TI  - PIK3CA, HRAS and PTEN in human papillomavirus positive oropharyngeal squamous 
      cell carcinoma.
PG  - 602
LID - 10.1186/1471-2407-13-602 [doi]
AB  - BACKGROUND: Recent genomic evidence suggests frequent phosphatidylinositide 
      3-kinase (PI3K) pathway activation in human papillomavirus (HPV) positive 
      oropharyngeal squamous cell carcinoma. Mutations/amplification of the gene 
      encoding p110alpha catalytic subunit of phosphoinositide 3-kinase (PIK3CA), loss of 
      phosphatase and tensin homolog (PTEN) and HRAS mutations are known to activate 
      PI3K pathway. METHODS AND RESULTS: PIK3CA mutations were identified by Sanger 
      sequencing in 23 of 75 (31%) HPV-positive oropharyngeal carcinomas, including 
      exon 9 (p.E545K [n = 10] and p.E542K [n = 5]) or exon 20 (p.H1047Y, n = 2) 
      mutations. Five rare and one novel (p.R537Q) PIK3CA mutations were identified. 
      HRAS mutation (p.Q61L) was detected in 1 of 62 tested cases. PIK3CA amplification 
      by fluorescence in situ hybridization (FISH) was identified in 4 cases (4/21, 
      20%), while PTEN loss was seen in 7 (7/21, 33%) cases (chromosome 10 monosomy [n 
      = 4], homozygous deletion [n = 3]). CONCLUSIONS: Overall, genetic alterations 
      that likely lead to PI3K pathway activation were identified in 34 of 75 cases 
      (45%) and did not correlate with disease specific survival. These findings offer 
      a molecular rationale for therapeutic targeting of PI3K pathway in patients with 
      HPV-positive oropharyngeal carcinoma.
FAU - Chiosea, Simion I
AU  - Chiosea SI
AD  - Department of Pathology, University of Pittsburgh, 200 Lothrop St, Pittsburgh, PA 
      15213, USA. chioseasi@upmc.edu.
FAU - Grandis, Jennifer R
AU  - Grandis JR
FAU - Lui, Vivian W Y
AU  - Lui VW
FAU - Diergaarde, Brenda
AU  - Diergaarde B
FAU - Maxwell, Jessica H
AU  - Maxwell JH
FAU - Ferris, Robert L
AU  - Ferris RL
FAU - Kim, Seungwon W
AU  - Kim SW
FAU - Luvison, Alyssa
AU  - Luvison A
FAU - Miller, Megan
AU  - Miller M
FAU - Nikiforova, Marina N
AU  - Nikiforova MN
LA  - eng
GR  - P50 CA097190/CA/NCI NIH HHS/United States
GR  - R01 CA098372/CA/NCI NIH HHS/United States
GR  - R01 DE023685/DE/NIDCR NIH HHS/United States
GR  - P50CA97190/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 - 20131217
PL  - England
TA  - BMC Cancer
JT  - BMC cancer
JID - 100967800
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.1.137 (Class I Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.1.137 (PIK3CA protein, human)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.6.5.2 (HRAS protein, human)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
SB  - IM
MH  - Adult
MH  - Aged
MH  - Carcinoma, Squamous Cell/*genetics/metabolism/mortality/pathology/*virology
MH  - Class I Phosphatidylinositol 3-Kinases
MH  - Exons
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Neoplasm Staging
MH  - Oropharyngeal Neoplasms/*genetics/metabolism/mortality/pathology/*virology
MH  - PTEN Phosphohydrolase/*genetics/metabolism
MH  - *Papillomaviridae
MH  - Papillomavirus Infections
MH  - Phosphatidylinositol 3-Kinases/*genetics/metabolism
MH  - Proto-Oncogene Proteins p21(ras)/*genetics/metabolism
MH  - Risk Factors
PMC - PMC3878565
EDAT- 2013/12/18 06:00
MHDA- 2014/06/24 06:00
PMCR- 2013/12/17
CRDT- 2013/12/18 06:00
PHST- 2013/06/02 00:00 [received]
PHST- 2013/12/06 00:00 [accepted]
PHST- 2013/12/18 06:00 [entrez]
PHST- 2013/12/18 06:00 [pubmed]
PHST- 2014/06/24 06:00 [medline]
PHST- 2013/12/17 00:00 [pmc-release]
AID - 1471-2407-13-602 [pii]
AID - 10.1186/1471-2407-13-602 [doi]
PST - epublish
SO  - BMC Cancer. 2013 Dec 17;13:602. doi: 10.1186/1471-2407-13-602.