G2Cdb::Human Disease report

Disease id
D00000028
Name
Lung cancer
Nervous system disease
no

Genes (6)

Gene Name/Description Mutations Found Literature Mutations Type Genetic association?
G00001624 PIK3CA
phosphoinositide-3-kinase, catalytic, alpha polypeptide
Y (15467468) Unknown (?) Y
G00001624 PIK3CA
phosphoinositide-3-kinase, catalytic, alpha polypeptide
Y (16930767) Microinsertion (MI) Y
G00002235 CTNNB1
catenin (cadherin-associated protein), beta 1, 88kDa
Y (11464291) Single nucleotide polymorphism (SNP) Y
G00002235 CTNNB1
catenin (cadherin-associated protein), beta 1, 88kDa
Y (11464291) Deletion (D) Y
G00001434 RAF1
v-raf-1 murine leukemia viral oncogene homolog 1
Y (7888083) No mutation found (N) N
G00000031 HRAS
v-Ha-ras Harvey rat sarcoma viral oncogene homolog
Y (8336750) Unknown (?) Y
G00001453 PTPN11
protein tyrosine phosphatase, non-receptor type 11
Y (15604238) Microinsertion (MI) Y
G00002124 AKAP9
A kinase (PRKA) anchor protein (yotiao) 9
Y (16741161) Single nucleotide polymorphism (SNP) Y

References

  • PIK3CA mutation status in Japanese lung cancer patients.

    Kawano O, Sasaki H, Endo K, Suzuki E, Haneda H, Yukiue H, Kobayashi Y, Yano M and Fujii Y

    Department of Surgery II, Nagoya City University Medical School, Nagoya, Japan.

    Somatic mutations of the PIK3CA (phosphatidylinostitol 3-kinase catalytic subunit) gene have been found in human cancer patients. Previous reports suggested that about 4% of lung cancers harbored PIK3CA gene mutations. However, the clinico-pathological background for PIK3CA gene mutations has not yet been investigated in lung cancer. We have genotyped the PIK3CA gene in Japanese lung cancer patients. The study included 235 lung cancer cases surgically removed in Nagoya City University Hospital. The two PIK3CA mutation hot spots (exon 9 and exon 20) were analyzed by real time polymerase chain reaction (PCR)-based assay. The data were confirmed by direct sequencing. In exon 9, somatic mutation was found in eight patients (3.4%). The mutation included three E542K (G1624A), three E545K (G1633A), one E542Q (G1624C), and one Q546K (C1636A). However, in exon 20, there was no mutation in our lung cancer patients. PIK3CA mutations were not correlated with gender (women versus men, p=0.4162), age (< or =60 versus >60, p=0.8027), or smoking status of the lung cancers (never versus smoker, p=0.5666). PIK3CA mutation incidence was significantly lower in adenocarcinoma (2/135, 1.5%) than in squamous cell carcinoma (5/77, 6.5%, p=0.0495). Among eight patients with a PIK3CA mutation, three patients also harbored an EGFR somatic mutation. PIK3CA gene mutations were rare in lung cancer; rarer in adenocarcinoma. Further functional analyses of the PIK3CA mutations are warranted to study if they could be the target of therapy for the lung cancer.

    Lung cancer (Amsterdam, Netherlands) 2006;54;2;209-15

  • Variants in the GH-IGF axis confer susceptibility to lung cancer.

    Rudd MF, Webb EL, Matakidou A, Sellick GS, Williams RD, Bridle H, Eisen T, Houlston RS and GELCAPS Consortium

    Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, UK.

    We conducted a large-scale genome-wide association study in UK Caucasians to identify susceptibility alleles for lung cancer, analyzing 1529 cases and 2707 controls. To increase the likelihood of identifying disease-causing alleles, we genotyped 1476 nonsynonymous single nucleotide polymorphisms (nsSNPs) in 871 candidate cancer genes, biasing SNP selection toward those predicted to be deleterious. Statistically significant associations were identified for 64 nsSNPs, generating a genome-wide significance level of P=0.002. Eleven of the 64 SNPs mapped to genes encoding pivotal components of the growth hormone/insulin-like growth factor (GH-IGF) pathway, including CAMKK1 E375G (OR=1.37, P=5.4x10(-5)), AKAP9 M463I (OR=1.32, P=1.0x10(-4)) and GHR P495T (OR=12.98, P=0.0019). Significant associations were also detected for SNPs within genes in the DNA damage-response pathway, including BRCA2 K3326X (OR=1.72, P=0.0075) and XRCC4 I137T (OR=1.31, P=0.0205). Our study provides evidence that inherited predisposition to lung cancer is in part mediated through low-penetrance alleles and specifically identifies variants in GH-IGF and DNA damage-response pathways with risk of lung cancer.

    Genome research 2006;16;6;693-701

  • Activating mutations of the noonan syndrome-associated SHP2/PTPN11 gene in human solid tumors and adult acute myelogenous leukemia.

    Bentires-Alj M, Paez JG, David FS, Keilhack H, Halmos B, Naoki K, Maris JM, Richardson A, Bardelli A, Sugarbaker DJ, Richards WG, Du J, Girard L, Minna JD, Loh ML, Fisher DE, Velculescu VE, Vogelstein B, Meyerson M, Sellers WR and Neel BG

    Cancer Biology Program, Department of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA. mbentire@bidmc.harvard.edu

    The SH2 domain-containing protein-tyrosine phosphatase PTPN11 (Shp2) is required for normal development and is an essential component of signaling pathways initiated by growth factors, cytokines, and extracellular matrix. In many of these pathways, Shp2 acts upstream of Ras. About 50% of patients with Noonan syndrome have germ-line PTPN11 gain of function mutations. Associations between Noonan syndrome and an increased risk of some malignancies, notably leukemia and neuroblastoma, have been reported, and recent data indicate that somatic PTPN11 mutations occur in children with sporadic juvenile myelomonocytic leukemia, myelodysplasic syndrome, B-cell acute lymphoblastic leukemia, and acute myelogenous leukemia (AML). Juvenile myelomonocytic leukemia patients without PTPN11 mutations have either homozygotic NF-1 deletion or activating RAS mutations. Given the role of Shp2 in Ras activation and the frequent mutation of RAS in human tumors, these data raise the possibility that PTPN11 mutations play a broader role in cancer. We asked whether PTPN11 mutations occur in other malignancies in which activating RAS mutations occur at low but significant frequency. Sequencing of PTPN11 from 13 different human neoplasms including breast, lung, gastric, and neuroblastoma tumors and adult AML and acute lymphoblastic leukemia revealed 11 missense mutations. Five are known mutations predicted to result in an activated form of Shp2, whereas six are new mutations. Biochemical analysis confirmed that several of the new mutations result in increased Shp2 activity. Our data demonstrate that mutations in PTPN11 occur at low frequency in several human cancers, especially neuroblastoma and AML, and suggest that Shp2 may be a novel target for antineoplastic therapy.

    Funded by: NCI NIH HHS: CA43460, R01 CA49152

    Cancer research 2004;64;24;8816-20

  • Oncogenic mutations of PIK3CA in human cancers.

    Samuels Y and Velculescu VE

    The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University Medical Institutions, Baltimore, Maryland 21231, USA.

    Phosphatidylinositol 3-kinases (PI3Ks) are important regulators of signaling pathways. To determine whether PI3Ks are genetically altered in human cancers, we recently analyzed the sequences of the PI3K gene family and discovered that one member, the PIK3CA gene encoding the p110alpha catalytic subunit, was frequently mutated in cancers of the colon, breast, brain and lung. The majority of mutations clustered near two positions within the PI3K helical or catalytic domains and at least one hotspot mutation appeared to increase kinase activity. PIK3CA represents one of the most highly mutated oncogenes identified in human cancers and may be a useful diagnostic and therapeutic target.

    Cell cycle (Georgetown, Tex.) 2004;3;10;1221-4

  • Genetic alteration of the beta-catenin gene (CTNNB1) in human lung cancer and malignant mesothelioma and identification of a new 3p21.3 homozygous deletion.

    Shigemitsu K, Sekido Y, Usami N, Mori S, Sato M, Horio Y, Hasegawa Y, Bader SA, Gazdar AF, Minna JD, Hida T, Yoshioka H, Imaizumi M, Ueda Y, Takahashi M and Shimokata K

    Department of Thoracic Surgery, Nagoya University School of Medicine, Nagoya 466-8550, Japan.

    The beta-catenin gene (CTNNB1) has been shown to be genetically mutated in various human malignancies. To determine whether the beta-catenin gene is responsible for oncogenesis in thoracic malignancies, we searched for the mutation in 166 lung cancers (90 primary tumors and 76 cell lines), one blastoma and 10 malignant mesotheliomas (two primary tumors and eight cell lines). Among the lung cancers, including 43 small cell lung cancers (SCLCs) and 123 non-small cell lung cancers (NSCLCs), we identified four alterations in exon 3, which is the target region of mutation for stabilizing beta-catenin. One primary adenocarcinoma had a somatic mutation from C to G, leading to an amino acid substitution from Ser to Cys at codon 37. Among the cell lines, SCLC NCI-H1092 had a mutation from A to G, leading to an Asp to Gly substitution at codon 6, NSCLC HCC15 had a mutation from C to T, leading to a Ser to Phe substitution at codon 45, and NSCLC NCI-H358 had a mutation from A to G, leading to a Thr to Ala substitution at codon 75. One blastoma also had a somatic mutation from C to G, leading to a Ser to Cys substitution at codon 37. Among the 10 malignant mesotheliomas, we identified a homozygous deletion in the NCI-H28 cell line. Cloning of the rearranged fragment from NCI-H28 indicated that all the exons except exon 1 of the beta-catenin gene are deleted and that the deletion junction is 13 kb downstream from exon 1. Furthermore, Northern blot analysis of 26 lung cancer and eight mesothelioma cell line RNAs detected ubiquitous expression of the beta-catenin messages except NCI-H28, although Western blot analysis showed that relatively less amounts of protein products were expressed in some of lung cancer cell lines. Our findings suggest that the beta-catenin gene is infrequently mutated in lung cancer and that the NCI-H28 homozygous deletion of the beta-catenin gene might indicate the possibility of a new tumor suppressor gene residing in this region at 3p21.3, where various types of human cancers show frequent allelic loss.

    Funded by: NCI NIH HHS: CA71618, P50 CA70907

    Oncogene 2001;20;31;4249-57

  • Absence of activating mutations of the RAF1 protooncogene in human lung cancer.

    Miwa W, Yasuda J, Yashima K, Makino R and Sekiya T

    Oncogene Division, National Cancer Center Research Institute, Tokyo, Japan.

    Recently, the RAF protein has been demonstrated to be a direct effector of RAS protein in a RAS-mediated signal transduction pathway. Activations of the RAF1 gene by small mutations, such as point mutations in the kinase domain and a tetrapeptide insertion into conserved region 2, have been suggested from analyses of chemically induced lung cancers in mice and by site-directed mutagenesis. We investigated the presence of small mutations of the RAF1 gene in human lung carcinomas, especially in those not carrying the mutated RAS gene, expecting that aberrations of the RAF1 gene might play a role complementary to RAS gene mutations in tumorigenesis. Single-strand conformation polymorphism (SSCP) analysis of polymerase chain reaction products of DNA samples from 140 patients revealed no tumor specific mutations of the RAF1 gene in any of these specimens. This result suggests that mutations of the RAF1 gene are not involved in tumorigenesis in human lung.

    Biological chemistry Hoppe-Seyler 1994;375;10;705-9

  • An association between the risk of cancer and mutations in the HRAS1 minisatellite locus.

    Krontiris TG, Devlin B, Karp DD, Robert NJ and Risch N

    Department of Medicine, Tufts University School of Medicine, Boston, MA.

    Background: The role of mutations in protooncogenes and their regulatory sequences in the pathogenesis of cancer is under close scrutiny. Minisatellites are unstable repetitive sequences of DNA that are present throughout the human genome. The highly polymorphic HRAS1 minisatellite locus just downstream from the protooncogene H-ras-1 consists of four common progenitor alleles and several dozen rare alleles, which apparently derive from mutations of the progenitors. We previously observed an association of the rare mutant alleles with many forms of cancer, and we undertook the present study to pursue this observation further.

    Methods: We conducted a case-control study, typing 736 HRAS1 alleles from patients with cancer and 652 from controls by Southern blotting of leukocyte DNA. We also carried out a meta-analysis of this study and 22 other published studies, estimating the relative risk of cancer (such as bladder, breast, or colorectal cancer) when one of the rare HRAS1 alleles was present.

    Results: Both the present case-control study (odds ratio, 1.83; 95 percent confidence interval, 1.28 to 2.67; P = 0.002) and the present study combined with our previous study (odds ratio, 2.07; 95 percent confidence interval, 1.47 to 2.92; P < 0.001), as well as the meta-analysis of all 23 studies (odds ratio, 1.93; 95 percent confidence interval, 1.63 to 2.30; chi-square = 57.58; P < 0.001), replicated our original finding and demonstrated a significant association of rare HRAS1 alleles with cancer. We found significant associations for four types of cancer: carcinomas of the breast, colorectum, and urinary bladder and acute leukemia. We also identified suggestive but not statistically significant associations for cancers of the lung and prostate and for non-Hodgkin's lymphoma.

    Conclusions: Mutant alleles of the HRAS1 minisatellite locus represent a major risk factor for common types of cancer. Although the relative risk associated with the presence of one rare allele is moderate, the aggregate prevalence of one rare allele is moderate, the aggregate prevalence of this class of mutant alleles implies an extremely important attributable risk: 1 in 11 cancers of the breast, colorectum, and bladder.

    Funded by: NCI NIH HHS: CA-45052

    The New England journal of medicine 1993;329;8;517-23

Literature (7)

Pubmed - human_disease

  • Variants in the GH-IGF axis confer susceptibility to lung cancer.

    Rudd MF, Webb EL, Matakidou A, Sellick GS, Williams RD, Bridle H, Eisen T, Houlston RS and GELCAPS Consortium

    Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, UK.

    We conducted a large-scale genome-wide association study in UK Caucasians to identify susceptibility alleles for lung cancer, analyzing 1529 cases and 2707 controls. To increase the likelihood of identifying disease-causing alleles, we genotyped 1476 nonsynonymous single nucleotide polymorphisms (nsSNPs) in 871 candidate cancer genes, biasing SNP selection toward those predicted to be deleterious. Statistically significant associations were identified for 64 nsSNPs, generating a genome-wide significance level of P=0.002. Eleven of the 64 SNPs mapped to genes encoding pivotal components of the growth hormone/insulin-like growth factor (GH-IGF) pathway, including CAMKK1 E375G (OR=1.37, P=5.4x10(-5)), AKAP9 M463I (OR=1.32, P=1.0x10(-4)) and GHR P495T (OR=12.98, P=0.0019). Significant associations were also detected for SNPs within genes in the DNA damage-response pathway, including BRCA2 K3326X (OR=1.72, P=0.0075) and XRCC4 I137T (OR=1.31, P=0.0205). Our study provides evidence that inherited predisposition to lung cancer is in part mediated through low-penetrance alleles and specifically identifies variants in GH-IGF and DNA damage-response pathways with risk of lung cancer.

    Genome research 2006;16;6;693-701

  • Activating mutations of the noonan syndrome-associated SHP2/PTPN11 gene in human solid tumors and adult acute myelogenous leukemia.

    Bentires-Alj M, Paez JG, David FS, Keilhack H, Halmos B, Naoki K, Maris JM, Richardson A, Bardelli A, Sugarbaker DJ, Richards WG, Du J, Girard L, Minna JD, Loh ML, Fisher DE, Velculescu VE, Vogelstein B, Meyerson M, Sellers WR and Neel BG

    Cancer Biology Program, Department of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA. mbentire@bidmc.harvard.edu

    The SH2 domain-containing protein-tyrosine phosphatase PTPN11 (Shp2) is required for normal development and is an essential component of signaling pathways initiated by growth factors, cytokines, and extracellular matrix. In many of these pathways, Shp2 acts upstream of Ras. About 50% of patients with Noonan syndrome have germ-line PTPN11 gain of function mutations. Associations between Noonan syndrome and an increased risk of some malignancies, notably leukemia and neuroblastoma, have been reported, and recent data indicate that somatic PTPN11 mutations occur in children with sporadic juvenile myelomonocytic leukemia, myelodysplasic syndrome, B-cell acute lymphoblastic leukemia, and acute myelogenous leukemia (AML). Juvenile myelomonocytic leukemia patients without PTPN11 mutations have either homozygotic NF-1 deletion or activating RAS mutations. Given the role of Shp2 in Ras activation and the frequent mutation of RAS in human tumors, these data raise the possibility that PTPN11 mutations play a broader role in cancer. We asked whether PTPN11 mutations occur in other malignancies in which activating RAS mutations occur at low but significant frequency. Sequencing of PTPN11 from 13 different human neoplasms including breast, lung, gastric, and neuroblastoma tumors and adult AML and acute lymphoblastic leukemia revealed 11 missense mutations. Five are known mutations predicted to result in an activated form of Shp2, whereas six are new mutations. Biochemical analysis confirmed that several of the new mutations result in increased Shp2 activity. Our data demonstrate that mutations in PTPN11 occur at low frequency in several human cancers, especially neuroblastoma and AML, and suggest that Shp2 may be a novel target for antineoplastic therapy.

    Funded by: NCI NIH HHS: CA43460, R01 CA49152

    Cancer research 2004;64;24;8816-20

  • Genetic alteration of the beta-catenin gene (CTNNB1) in human lung cancer and malignant mesothelioma and identification of a new 3p21.3 homozygous deletion.

    Shigemitsu K, Sekido Y, Usami N, Mori S, Sato M, Horio Y, Hasegawa Y, Bader SA, Gazdar AF, Minna JD, Hida T, Yoshioka H, Imaizumi M, Ueda Y, Takahashi M and Shimokata K

    Department of Thoracic Surgery, Nagoya University School of Medicine, Nagoya 466-8550, Japan.

    The beta-catenin gene (CTNNB1) has been shown to be genetically mutated in various human malignancies. To determine whether the beta-catenin gene is responsible for oncogenesis in thoracic malignancies, we searched for the mutation in 166 lung cancers (90 primary tumors and 76 cell lines), one blastoma and 10 malignant mesotheliomas (two primary tumors and eight cell lines). Among the lung cancers, including 43 small cell lung cancers (SCLCs) and 123 non-small cell lung cancers (NSCLCs), we identified four alterations in exon 3, which is the target region of mutation for stabilizing beta-catenin. One primary adenocarcinoma had a somatic mutation from C to G, leading to an amino acid substitution from Ser to Cys at codon 37. Among the cell lines, SCLC NCI-H1092 had a mutation from A to G, leading to an Asp to Gly substitution at codon 6, NSCLC HCC15 had a mutation from C to T, leading to a Ser to Phe substitution at codon 45, and NSCLC NCI-H358 had a mutation from A to G, leading to a Thr to Ala substitution at codon 75. One blastoma also had a somatic mutation from C to G, leading to a Ser to Cys substitution at codon 37. Among the 10 malignant mesotheliomas, we identified a homozygous deletion in the NCI-H28 cell line. Cloning of the rearranged fragment from NCI-H28 indicated that all the exons except exon 1 of the beta-catenin gene are deleted and that the deletion junction is 13 kb downstream from exon 1. Furthermore, Northern blot analysis of 26 lung cancer and eight mesothelioma cell line RNAs detected ubiquitous expression of the beta-catenin messages except NCI-H28, although Western blot analysis showed that relatively less amounts of protein products were expressed in some of lung cancer cell lines. Our findings suggest that the beta-catenin gene is infrequently mutated in lung cancer and that the NCI-H28 homozygous deletion of the beta-catenin gene might indicate the possibility of a new tumor suppressor gene residing in this region at 3p21.3, where various types of human cancers show frequent allelic loss.

    Funded by: NCI NIH HHS: CA71618, P50 CA70907

    Oncogene 2001;20;31;4249-57

  • Absence of activating mutations of the RAF1 protooncogene in human lung cancer.

    Miwa W, Yasuda J, Yashima K, Makino R and Sekiya T

    Oncogene Division, National Cancer Center Research Institute, Tokyo, Japan.

    Recently, the RAF protein has been demonstrated to be a direct effector of RAS protein in a RAS-mediated signal transduction pathway. Activations of the RAF1 gene by small mutations, such as point mutations in the kinase domain and a tetrapeptide insertion into conserved region 2, have been suggested from analyses of chemically induced lung cancers in mice and by site-directed mutagenesis. We investigated the presence of small mutations of the RAF1 gene in human lung carcinomas, especially in those not carrying the mutated RAS gene, expecting that aberrations of the RAF1 gene might play a role complementary to RAS gene mutations in tumorigenesis. Single-strand conformation polymorphism (SSCP) analysis of polymerase chain reaction products of DNA samples from 140 patients revealed no tumor specific mutations of the RAF1 gene in any of these specimens. This result suggests that mutations of the RAF1 gene are not involved in tumorigenesis in human lung.

    Biological chemistry Hoppe-Seyler 1994;375;10;705-9

  • An association between the risk of cancer and mutations in the HRAS1 minisatellite locus.

    Krontiris TG, Devlin B, Karp DD, Robert NJ and Risch N

    Department of Medicine, Tufts University School of Medicine, Boston, MA.

    Background: The role of mutations in protooncogenes and their regulatory sequences in the pathogenesis of cancer is under close scrutiny. Minisatellites are unstable repetitive sequences of DNA that are present throughout the human genome. The highly polymorphic HRAS1 minisatellite locus just downstream from the protooncogene H-ras-1 consists of four common progenitor alleles and several dozen rare alleles, which apparently derive from mutations of the progenitors. We previously observed an association of the rare mutant alleles with many forms of cancer, and we undertook the present study to pursue this observation further.

    Methods: We conducted a case-control study, typing 736 HRAS1 alleles from patients with cancer and 652 from controls by Southern blotting of leukocyte DNA. We also carried out a meta-analysis of this study and 22 other published studies, estimating the relative risk of cancer (such as bladder, breast, or colorectal cancer) when one of the rare HRAS1 alleles was present.

    Results: Both the present case-control study (odds ratio, 1.83; 95 percent confidence interval, 1.28 to 2.67; P = 0.002) and the present study combined with our previous study (odds ratio, 2.07; 95 percent confidence interval, 1.47 to 2.92; P < 0.001), as well as the meta-analysis of all 23 studies (odds ratio, 1.93; 95 percent confidence interval, 1.63 to 2.30; chi-square = 57.58; P < 0.001), replicated our original finding and demonstrated a significant association of rare HRAS1 alleles with cancer. We found significant associations for four types of cancer: carcinomas of the breast, colorectum, and urinary bladder and acute leukemia. We also identified suggestive but not statistically significant associations for cancers of the lung and prostate and for non-Hodgkin's lymphoma.

    Conclusions: Mutant alleles of the HRAS1 minisatellite locus represent a major risk factor for common types of cancer. Although the relative risk associated with the presence of one rare allele is moderate, the aggregate prevalence of one rare allele is moderate, the aggregate prevalence of this class of mutant alleles implies an extremely important attributable risk: 1 in 11 cancers of the breast, colorectum, and bladder.

    Funded by: NCI NIH HHS: CA-45052

    The New England journal of medicine 1993;329;8;517-23

Pubmed - other

  • PIK3CA mutation status in Japanese lung cancer patients.

    Kawano O, Sasaki H, Endo K, Suzuki E, Haneda H, Yukiue H, Kobayashi Y, Yano M and Fujii Y

    Department of Surgery II, Nagoya City University Medical School, Nagoya, Japan.

    Somatic mutations of the PIK3CA (phosphatidylinostitol 3-kinase catalytic subunit) gene have been found in human cancer patients. Previous reports suggested that about 4% of lung cancers harbored PIK3CA gene mutations. However, the clinico-pathological background for PIK3CA gene mutations has not yet been investigated in lung cancer. We have genotyped the PIK3CA gene in Japanese lung cancer patients. The study included 235 lung cancer cases surgically removed in Nagoya City University Hospital. The two PIK3CA mutation hot spots (exon 9 and exon 20) were analyzed by real time polymerase chain reaction (PCR)-based assay. The data were confirmed by direct sequencing. In exon 9, somatic mutation was found in eight patients (3.4%). The mutation included three E542K (G1624A), three E545K (G1633A), one E542Q (G1624C), and one Q546K (C1636A). However, in exon 20, there was no mutation in our lung cancer patients. PIK3CA mutations were not correlated with gender (women versus men, p=0.4162), age (< or =60 versus >60, p=0.8027), or smoking status of the lung cancers (never versus smoker, p=0.5666). PIK3CA mutation incidence was significantly lower in adenocarcinoma (2/135, 1.5%) than in squamous cell carcinoma (5/77, 6.5%, p=0.0495). Among eight patients with a PIK3CA mutation, three patients also harbored an EGFR somatic mutation. PIK3CA gene mutations were rare in lung cancer; rarer in adenocarcinoma. Further functional analyses of the PIK3CA mutations are warranted to study if they could be the target of therapy for the lung cancer.

    Lung cancer (Amsterdam, Netherlands) 2006;54;2;209-15

  • Oncogenic mutations of PIK3CA in human cancers.

    Samuels Y and Velculescu VE

    The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University Medical Institutions, Baltimore, Maryland 21231, USA.

    Phosphatidylinositol 3-kinases (PI3Ks) are important regulators of signaling pathways. To determine whether PI3Ks are genetically altered in human cancers, we recently analyzed the sequences of the PI3K gene family and discovered that one member, the PIK3CA gene encoding the p110alpha catalytic subunit, was frequently mutated in cancers of the colon, breast, brain and lung. The majority of mutations clustered near two positions within the PI3K helical or catalytic domains and at least one hotspot mutation appeared to increase kinase activity. PIK3CA represents one of the most highly mutated oncogenes identified in human cancers and may be a useful diagnostic and therapeutic target.

    Cell cycle (Georgetown, Tex.) 2004;3;10;1221-4

© G2C 2014. The Genes to Cognition Programme received funding from The Wellcome Trust and the EU FP7 Framework Programmes:
EUROSPIN (FP7-HEALTH-241498), SynSys (FP7-HEALTH-242167) and GENCODYS (FP7-HEALTH-241995).

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