Gliomas are the most common of the primary brain tumors and account for more than 40% of all central nervous system neoplasms. Gliomas include tumours that are composed predominantly of astrocytes (astrocytomas), oligodendrocytes (oligodendrogliomas), mixtures of various glial cells (for example,oligoastrocytomas) and ependymal cells (ependymomas). The most malignant form of infiltrating astrocytoma - glioblastoma multiforme (GBM) - is one of the most aggressive human cancers. GBM may develop de novo (primary glioblastoma) or by progression from low-grade or anaplastic astrocytoma (secondary glioblastoma). Primary glioblastomas develop in older patients and typically show genetic alterations (EGFR amplification, p16/INK4a deletion, and PTEN mutations) at frequencies of 24-34%. Secondary glioblastomas develop in younger patients and frequently show overexpression of PDGF and CDK4 as well as p53 mutations (65%) and loss of Rb playing major roles in such transformations. Loss of PTEN has been implicated in both pathways, although it is much more common in the pathogenesis of primary GBM.
Category
Cancer
Brite
Human diseases in ICD-11 classification [BR:br08403]
02 Neoplasms
Neoplasms of brain or central nervous system
2A00 Primary neoplasms of brain
H00042 Glioma
Pathway-based classification of diseases [BR:br08402]
Signal transduction
nt06526 MAPK signaling
H00042 Glioma
nt06528 Calcium signaling
H00042 Glioma
Cancer-associated carbohydrates [br08441.html]
H00042
Zheng H, Ying H, Yan H, Kimmelman AC, Hiller DJ, Chen AJ, Perry SR, Tonon G, Chu GC, Ding Z, Stommel JM, Dunn KL, Wiedemeyer R, You MJ, Brennan C, Wang YA, Ligon KL, Wong WH, Chin L, DePinho RA
Title
p53 and Pten control neural and glioma stem/progenitor cell renewal and differentiation.
Staal FJ, van der Luijt RB, Baert MR, van Drunen J, van Bakel H, Peters E, de Valk I, van Amstel HK, Taphoorn MJ, Jansen GH, van Veelen CW, Burgering B, Staal GE
Title
A novel germline mutation of PTEN associated with brain tumours of multiple lineages.
Lung cancer is a leading cause of cancer death among men and women in industrialized countries. Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer and represents a heterogeneous group of cancers, consisting mainly of squamous cell (SCC), adeno (AC) and large-cell carcinoma. Molecular mechanisms altered in NSCLC include activation of oncogenes, such as K-RAS, EGFR and EML4-ALK, and inactivation of tumorsuppressor genes, such as p53, p16INK4a, RAR-beta, and RASSF1. Point mutations within the K-RAS gene inactivate GTPase activity and the p21-RAS protein continuously transmits growth signals to the nucleus. Mutations or overexpression of EGFR leads to a proliferative advantage. EML4-ALK fusion leads to constitutive ALK activation, which causes cell proliferation, invasion, and inhibition of apoptosis. Inactivating mutation of p53 can lead to more rapid proliferation and reduced apoptosis. The protein encoded by the p16INK4a inhibits formation of CDK-cyclin-D complexes by competitive binding of CDK4 and CDK6. Loss of p16INK4a expression is a common feature of NSCLC. RAR-beta is a nuclear receptor that bears vitamin-A-dependent transcriptional activity. RASSF1A is able to form heterodimers with Nore-1, an RAS effector. Therefore loss of RASSF1A might shift the balance of RAS activity towards a growth-promoting effect.
Category
Cancer
Brite
Human diseases in ICD-11 classification [BR:br08403]
02 Neoplasms
Malignant neoplasms, except primary neoplasms of lymphoid, haematopoietic, central nervous system or related tissues
Malignant neoplasms, stated or presumed to be primary, of specified sites, except of lymphoid, haematopoietic, central nervous system or related tissues
Malignant neoplasms of middle ear, respiratory or intrathoracic organs
2C25 Malignant neoplasms of bronchus or lung
H00014 Non-small cell lung cancer
Pathway-based classification of diseases [BR:br08402]
Signal transduction
nt06526 MAPK signaling
H00014 Non-small cell lung cancer
nt06528 Calcium signaling
H00014 Non-small cell lung cancer
nt06543 NRG-ERBB signaling
H00014 Non-small cell lung cancer
Cellular process
nt06512 Chromosome cohesion and segregation
H00014 Non-small cell lung cancer
Tumor markers [br08442.html]
H00014
Cancer-associated carbohydrates [br08441.html]
H00014
Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S, Fujiwara S, Watanabe H, Kurashina K, Hatanaka H, Bando M, Ohno S, Ishikawa Y, Aburatani H, Niki T, Sohara Y, Sugiyama Y, Mano H
Title
Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer.
Takeuchi K, Soda M, Togashi Y, Suzuki R, Sakata S, Hatano S, Asaka R, Hamanaka W, Ninomiya H, Uehara H, Lim Choi Y, Satoh Y, Okumura S, Nakagawa K, Mano H, Ishikawa Y
Burbee DG, Forgacs E, Zochbauer-Muller S, Shivakumar L, Fong K, Gao B, Randle D, Kondo M, Virmani A, Bader S, Sekido Y, Latif F, Milchgrub S, Toyooka S, Gazdar AF, Lerman MI, Zabarovsky E, White M, Minna JD
Title
Epigenetic inactivation of RASSF1A in lung and breast cancers and malignant phenotype suppression.
Tam IY, Chung LP, Suen WS, Wang E, Wong MC, Ho KK, Lam WK, Chiu SW, Girard L, Minna JD, Gazdar AF, Wong MP
Title
Distinct epidermal growth factor receptor and KRAS mutation patterns in non-small cell lung cancer patients with different tobacco exposure and clinicopathologic features.
Hayashi N, Sugimoto Y, Tsuchiya E, Ogawa M, Nakamura Y
Title
Somatic mutations of the MTS (multiple tumor suppressor) 1/CDK4l (cyclin-dependent kinase-4 inhibitor) gene in human primary non-small cell lung carcinomas.
