PTEN mutations and relationship to EGFR, ERBB2, KRAS, and TP53 mutations in non-small cell lung cancers.

Somatic mutations of phosphatase and tensin homolog deleted on chromosome ten (PTEN) in non-small cell lung cancers (NSCLCs) have been investigated in but a small number of cases. In addition, the relationship between PTEN mutations and epidermal growth factor receptor (EGFR), KRAS, and TP53 mutations has not been investigated. Therefore, we investigated the frequency of PTEN mutations in 176 surgically resected NSCLCs and analyzed the relationship between PTEN mutations and EGFR, ERBB2, KRAS, and TP53 mutations. Mutations of PTEN (exons 1-9), EGFR (exons 18-21), ERBB2 (exons 19 and 20), KRAS (exon 1), and TP53 (exons 2-11) were determined by polymerase chain reaction and direct sequencing. PTEN mutations were present in 8 (4.5%) of the 176 tumors. PTEN mutations were only found in ever-smokers and were significantly more frequent in squamous cell carcinoma than in adenocarcinoma (10.2% vs 1.7%, P=0.02). Mutations of EGFR, ERBB2, KRAS, and TP53 genes were found in 36 (20.5%), 2 (1.1%), 11 (6.3%), and 66 (37.5%) cases, respectively. Of the 8 tumors with PTEN mutations, 1 case concurrently had an EGFR mutation and 4 cases had TP53 mutations. However, PTEN mutations were not found in the tumors with KRAS mutation. Our findings indicate that PTEN mutations are relatively common in NSCLC, and thus analysis of PTEN mutations may facilitate a comprehensive understanding of the genetic alterations related to the EGFR signaling pathway.

Jin G ，Kim MJ ，Jeon HS ，Choi JE ，Kim DS ，Lee EB ，Cha SI ，Yoon GS ，Kim CH ，Jung TH ，Park JY ... -  《-》

Somatic mutations in epidermal growth factor receptor signaling pathway genes in non-small cell lung cancers.

Lee SY ，Kim MJ ，Jin G ，Yoo SS ，Park JY ，Choi JE ，Jeon HS ，Cho S ，Lee EB ，Cha SI ，Park TI ，Kim CH ，Jung TH ，Park JY ... -  《-》

Using whole genome amplification (WGA) of low-volume biopsies to assess the prognostic role of EGFR, KRAS, p53, and CMET mutations in advanced-stage non-small cell lung cancer (NSCLC).

Lim EH ，Zhang SL ，Li JL ，Yap WS ，Howe TC ，Tan BP ，Lee YS ，Wong D ，Khoo KL ，Seto KY ，Tan L ，Agasthian T ，Koong HN ，Tam J ，Tan C ，Caleb M ，Chang A ，Ng A ，Tan P ... -  《-》

Mutation of TP53 and alteration of p14(arf) expression in EGFR- and KRAS-mutated lung adenocarcinomas.

In lung adenocarcinoma, inactivation of the tumor suppressor p53 may abrogate a safeguard mechanism preventing the development of tumors with activating mutations in EGFR or KRAS. To assess this hypothesis, we analyzed TP53 mutations and downregulation of p14(arf), a negative regulator of p53 activated by oncogenic signals, in a retrospective series of 96 patients with primary adenocarcinoma of the lung. Mutations in TP53 (exons 4-9), KRAS (exon 1), and EGFR (exons 18-21) were identified by direct sequencing of DNA from formalin-fixed, paraffin-embedded resected tumors. Expression of p14(arf) was semiquantitatively evaluated by immunohistochemical analysis. TP53, KRAS, and EGFR mutations were detected in 42 of 93 (45.2%), 15 of 95 (15.8%), and 31 of 90 (34.4%) cases, respectively. Low p14(arf) expression was observed in 19 of 91 cases (20.9%). Disruption of the p53/p14(arf) pathway (defined as TP53 mutation or decreased p14(arf) expression, or both) was observed in 18 of 31 EGFR-mutated (58.1%) tumors and in 9 of 13 KRAS-mutated (69.2%) tumors. Inactivation of the p53/p14(arf) pathway is common but not systematic in EGFR- or KRAS-mutated lung adenocarcinomas. Our work highlights the need to better investigate the association between EGFR and KRAS mutations and alterations in tumor suppressor pathways.

Cortot AB ，Younes M ，Martel-Planche G ，Guibert B ，Isaac S ，Souquet PJ ，Commo F ，Girard P ，Fouret P ，Brambilla E ，Hainaut P ，Soria JC ... -  《-》

EGFR, ERBB2, and KRAS mutations in Korean non-small cell lung cancer patients.

Bae NC ，Chae MH ，Lee MH ，Kim KM ，Lee EB ，Kim CH ，Park TI ，Han SB ，Jheon S ，Jung TH ，Park JY ... -  《cancer genetics and cytogenetics》