Frequent alterations of the PI3K/AKT/mTOR pathways in hereditary nonpolyposis colorectal cancer.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Standard

Frequent alterations of the PI3K/AKT/mTOR pathways in hereditary nonpolyposis colorectal cancer. / Isinger Ekstrand, Anna; Jönsson, Mats; Lindblom, Annika; Borg, Åke; Nilbert, Mef.

I: Familial Cancer, Vol. 9, 2010, s. 125-129.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

APA

CBE

MLA

Vancouver

Author

RIS

TY - JOUR

T1 - Frequent alterations of the PI3K/AKT/mTOR pathways in hereditary nonpolyposis colorectal cancer.

AU - Isinger Ekstrand, Anna

AU - Jönsson, Mats

AU - Lindblom, Annika

AU - Borg, Åke

AU - Nilbert, Mef

PY - 2010

Y1 - 2010

N2 - The phosphatidylinositol 3-kinases-AKT-mammalian target of rapamycin pathway (PI3K/AKT/mTOR) is central in colorectal tumors. Data on its role in hereditary cancers are, however, scarce and we therefore characterized mutations in PIK3CA and KRAS, and expression of PIK3CA, phosphorylated AKT, and PTEN in colorectal cancers linked to hereditary nonpolyposis colorectal cancer (HNPCC). Sequencing was used to identify mutations in PIK3CA, a real-time PCR-based method to identify KRAS mutations, and immunohistochemical staining was used to evaluate the expression of PIK3CA, phosphorylated AKT and PTEN in 58 HNPCC-associated colorectal cancers. Derangements of at least one of the PI3K/AKT/mTOR components analyzed were found in 51/58 (88%) tumors. Mutations in PIK3CA and KRAS were identified in 14 and 31% of the tumors respectively. Overexpression of PIK3CA and phosphorylated AKT occurred in 59 and 75% and were strongly associated (P = 0.005). Reduced/lost PTEN expression was found in 63% of the tumors. Though HNPCC-associated colorectal cancers show simple genetic profiles with few chromosomal alterations, we demonstrate frequent and repeated targeting of the PI3K/AKT/mTOR pathway, which suggests that therapeutic strategies directed at this pathway are likely to be beneficial also in HNPCC.

AB - The phosphatidylinositol 3-kinases-AKT-mammalian target of rapamycin pathway (PI3K/AKT/mTOR) is central in colorectal tumors. Data on its role in hereditary cancers are, however, scarce and we therefore characterized mutations in PIK3CA and KRAS, and expression of PIK3CA, phosphorylated AKT, and PTEN in colorectal cancers linked to hereditary nonpolyposis colorectal cancer (HNPCC). Sequencing was used to identify mutations in PIK3CA, a real-time PCR-based method to identify KRAS mutations, and immunohistochemical staining was used to evaluate the expression of PIK3CA, phosphorylated AKT and PTEN in 58 HNPCC-associated colorectal cancers. Derangements of at least one of the PI3K/AKT/mTOR components analyzed were found in 51/58 (88%) tumors. Mutations in PIK3CA and KRAS were identified in 14 and 31% of the tumors respectively. Overexpression of PIK3CA and phosphorylated AKT occurred in 59 and 75% and were strongly associated (P = 0.005). Reduced/lost PTEN expression was found in 63% of the tumors. Though HNPCC-associated colorectal cancers show simple genetic profiles with few chromosomal alterations, we demonstrate frequent and repeated targeting of the PI3K/AKT/mTOR pathway, which suggests that therapeutic strategies directed at this pathway are likely to be beneficial also in HNPCC.

U2 - 10.1007/s10689-009-9293-1

DO - 10.1007/s10689-009-9293-1

M3 - Article

C2 - 19731079

VL - 9

SP - 125

EP - 129

JO - Familial Cancer

JF - Familial Cancer

SN - 1389-9600

ER -