Chiosea, SI and Grandis, JR and Lui, VWY and Diergaarde, B and Maxwell, JH and Ferris, RL and Kim, SW and Luvison, A and Miller, M and Nikiforova, MN
(2013)
PIK3CA, HRAS and PTEN in human papillomavirus positive oropharyngeal squamous cell carcinoma.
BMC Cancer, 13.
Abstract
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 p110α 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. © 2013 Chiosea et al.; licensee BioMed Central Ltd.
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| Item Type: |
Article
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| Status: |
Published |
| Creators/Authors: |
| Creators | Email | Pitt Username | ORCID  |
|---|
| Chiosea, SI | sic5@pitt.edu | SIC5 | | | Grandis, JR | jgrandis@pitt.edu | JGRANDIS | | | Lui, VWY | | | | | Diergaarde, B | bbd3@pitt.edu | BBD3 | | | Maxwell, JH | | | | | Ferris, RL | rlf1@pitt.edu | RLF1 | | | Kim, SW | swk7@pitt.edu | SWK7 | | | Luvison, A | | | | | Miller, M | | | | | Nikiforova, MN | mnn4@pitt.edu | MNN4 | |
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| Date: |
17 December 2013 |
| Date Type: |
Publication |
| Journal or Publication Title: |
BMC Cancer |
| Volume: |
13 |
| DOI or Unique Handle: |
10.1186/1471-2407-13-602 |
| Schools and Programs: |
School of Medicine > Otolaryngology
School of Medicine > Pathology |
| Refereed: |
Yes |
| Date Deposited: |
02 Dec 2016 18:30 |
| Last Modified: |
02 Feb 2019 16:58 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/29633 |
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