Multiple pathways leading to genomic instability and tumorigenesis
- Univ. of Vermont, Burlington, VT (United States)
Genome instability is a hallmark of many cancers and is thought to play a role in tumorigenesis. Several types of genomic alterations have been described in various tumor cell lines, including expansion and contraction of microsatellite sequences and gross chromosomal rearrangements such as translocations, deletions, and gene amplification events. Several lines of evidence implicate a role for genome instability in the development of neoplasias as well as tumor progression. In hereditary nonpolyposis colon cancer (HNPCC), the instability of microsatellite sequences throughout the genome of tumors has been observed. Furthermore, microsatellite instability has been observed in 20-30% of ovarian, gastric, pancreatic, prostate, and lung tumors, and occurs at a very early stage in the development of sporadic endometrial tumors. Chromosomal translocations have been implicated in oncogene activation in several lymphomas. Barrett`s esophagus is a condition in which the progression into a cancerous state appears to proceed through a loss of cell cycle regulation, to genetic instability, and finally to the production of a solid tumor. In addition, other cancer-prone syndromes such as ataxia telangiectasia display an increase in chromosomal translocations and a loss of cell cycle regulation. The biochemical activities involved in the generation of these alterations are poorly understood and the subject of a great deal of debate. Defects in several aspects of DNA metabolism and cell cycle regulation have been proposed to be involved in the alteration of chromosomal structure. Here we discuss the possibility that several pathways exist that could lead to the development of genome instability, a higher than normal mutation rate, and the development of tumor cells.
- Research Organization:
- New York Academy of Sciences, New York, NY (United States)
- OSTI ID:
- 134846
- Report Number(s):
- CONF-9307221-; TRN: 95:007741-0012
- Resource Relation:
- Conference: DNA damage: effects on DNA structure and protein recognition, Burlington, VT (United States), 31 Jul - 4 Aug 1993; Other Information: PBD: 1994; Related Information: Is Part Of DNA damage: Effects on DNA structure and protein recognition; Wallace, S.S.; Van Houten, B.; Kow, Yoke Wah [eds.]; PB: 395 p.
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
BASIC STUDIES
ONCOGENES
INSTABILITY
GENE AMPLIFICATION
GENE REGULATION
GENE RECOMBINATION
TUMOR CELLS
CELL CYCLE
DNA
ONCOGENIC TRANSFORMATIONS
METABOLISM
DNA REPLICATION
HUMAN CHROMOSOMES
CHROMOSOMAL ABERRATIONS
STRUCTURE-ACTIVITY RELATIONSHIPS
MUTATION FREQUENCY
HUMAN POPULATIONS
GENOME MUTATIONS
NEOPLASMS
HEREDITARY DISEASES
DIGESTIVE SYSTEM DISEASES
TELANGIECTASIS
NERVOUS SYSTEM DISEASES
PHENOTYPE
NUCLEOTIDES
DNA POLYMERASES