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PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma

Saal, Lao LU ; Holm, Karolina LU ; Maurer, M; Memeo, L; Su, T; Wang, XM; Yu, JS; Malmström, Per LU ; Mansukhani, M and Enoksson, Jens LU , et al. (2005) In Cancer Research 65(7). p.2554-2559
Abstract
Deregulation of the phosphatidylinositol 3-kinase (PI3K) pathway either through loss of PTEN or mutation of the catalytic subunit alpha of PI3K (PIK3CA) occurs frequently in human cancer. We identified PIK3CA mutations in 26% of 342 human breast tumor samples and cell lines at about equal frequency in tumor stages I to IV. To investigate the relationship between PTEN and PIK3CA, we generated a cohort of tumors that had lost PTEN expression and compared it with a matched control set that had retained PTEN. A highly significant association between PIK3CA mutations and retention of PTEN protein expression was observed. In addition, PIK3CA mutations were associated with expression of estrogen and progesterone receptors (ER/PR), lymph node... (More)
Deregulation of the phosphatidylinositol 3-kinase (PI3K) pathway either through loss of PTEN or mutation of the catalytic subunit alpha of PI3K (PIK3CA) occurs frequently in human cancer. We identified PIK3CA mutations in 26% of 342 human breast tumor samples and cell lines at about equal frequency in tumor stages I to IV. To investigate the relationship between PTEN and PIK3CA, we generated a cohort of tumors that had lost PTEN expression and compared it with a matched control set that had retained PTEN. A highly significant association between PIK3CA mutations and retention of PTEN protein expression was observed. In addition, PIK3CA mutations were associated with expression of estrogen and progesterone receptors (ER/PR), lymph node metastasis, and ERBB2 overexpression. The fact that PIK3CA mutations and PTEN loss are nearly mutually exclusive implies that deregulated phosphatidylinositol-3,4,5-triphosphate WIN is critical for tumorigenesis in a significant fraction of breast cancers and that loss Of PIP3 homeostasis by abrogation of either PIK3CA or PTEN relieves selective pressure for targeting of the other gene. The correlation of PIK3CA mutation to ER/PR-positive tumors and PTEN loss to ER/PR-negative tumors argues for disparate branches of tumor evolution. Furthermore, the association between ERBB2 overexpression and PIK3CA mutation implies that more than one input activating the PI3K/AKT pathway may be required to overcome intact PTEN. Thus, mutation of PIK3CA is frequent, occurs early in carcinoma development, and has prognostic and therapeutic implications. (Less)
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Cancer Research
volume
65
issue
7
pages
2554 - 2559
publisher
American Association for Cancer Research Inc.
external identifiers
  • wos:000227972300010
  • pmid:15805248
ISSN
1538-7445
language
English
LU publication?
yes
id
3f56566f-3581-485f-b526-a6c4cceaf8d7 (old id 247152)
alternative location
http://cancerres.aacrjournals.org/cgi/content/full/65/7/2554
date added to LUP
2007-08-22 15:56:50
date last changed
2016-04-16 04:27:26
@article{3f56566f-3581-485f-b526-a6c4cceaf8d7,
  abstract     = {Deregulation of the phosphatidylinositol 3-kinase (PI3K) pathway either through loss of PTEN or mutation of the catalytic subunit alpha of PI3K (PIK3CA) occurs frequently in human cancer. We identified PIK3CA mutations in 26% of 342 human breast tumor samples and cell lines at about equal frequency in tumor stages I to IV. To investigate the relationship between PTEN and PIK3CA, we generated a cohort of tumors that had lost PTEN expression and compared it with a matched control set that had retained PTEN. A highly significant association between PIK3CA mutations and retention of PTEN protein expression was observed. In addition, PIK3CA mutations were associated with expression of estrogen and progesterone receptors (ER/PR), lymph node metastasis, and ERBB2 overexpression. The fact that PIK3CA mutations and PTEN loss are nearly mutually exclusive implies that deregulated phosphatidylinositol-3,4,5-triphosphate WIN is critical for tumorigenesis in a significant fraction of breast cancers and that loss Of PIP3 homeostasis by abrogation of either PIK3CA or PTEN relieves selective pressure for targeting of the other gene. The correlation of PIK3CA mutation to ER/PR-positive tumors and PTEN loss to ER/PR-negative tumors argues for disparate branches of tumor evolution. Furthermore, the association between ERBB2 overexpression and PIK3CA mutation implies that more than one input activating the PI3K/AKT pathway may be required to overcome intact PTEN. Thus, mutation of PIK3CA is frequent, occurs early in carcinoma development, and has prognostic and therapeutic implications.},
  author       = {Saal, Lao and Holm, Karolina and Maurer, M and Memeo, L and Su, T and Wang, XM and Yu, JS and Malmström, Per and Mansukhani, M and Enoksson, Jens and Hibshoosh, H and Borg, Åke and Parsons, R},
  issn         = {1538-7445},
  language     = {eng},
  number       = {7},
  pages        = {2554--2559},
  publisher    = {American Association for Cancer Research Inc.},
  series       = {Cancer Research},
  title        = {PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma},
  volume       = {65},
  year         = {2005},
}