ras oncogenes in human cancer: a review.

Mutations in codon 12, 13, or 61 of one of the three ras genes, H-ras, K-ras, and N-ras, convert these genes into active oncogenes. Rapid assays for the detection of these point mutations have been developed recently and used to investigate the role mutated ras genes play in the pathogenesis of human tumors. It appeared that ras gene mutations can be found in a variety of tumor types, although the incidence varies greatly. The highest incidences are found in adenocarcinomas of the pancreas (90%), the colon (50%), and the lung (30%); in thyroid tumors (50%); and in myeloid leukemia (30%). For some tumor types a relationship may exist between the presence of a ras mutation and clinical or histopathological features of the tumor. There is some evidence that environmental agents may be involved in the induction of the mutations.

[1]  J. Bos,et al.  Activated ras genes in human seminoma: evidence for tumor heterogeneity. , 1989, Oncogene.

[2]  C. Bartram,et al.  High frequency of Ki‐ras codon 12 mutations in pancreatic adenocarcinomas , 1989, International journal of cancer.

[3]  W. Hiddemann,et al.  Acute myeloid leukemia: analysis of ras gene mutations and clonality defined by polymorphic X-linked loci. , 1989, Leukemia.

[4]  N. Lemoine,et al.  High frequency of ras oncogene activation in all stages of human thyroid tumorigenesis. , 1989, Oncogene.

[5]  Frank McCormick,et al.  ras GTPase activating protein: Signal transmitter and signal terminator , 1989, Cell.

[6]  F. McCormick,et al.  Analysis of RAS oncogene mutations in human lymphoid malignancies. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[7]  C. Marshall,et al.  A study of ras gene mutations in colonic adenomas from familial polyposis coli patients. , 1988, Oncogene.

[8]  H. Drexler,et al.  Evidence for pluripotent stem cell origin of idiopathic myelofibrosis: clonal analysis of a case characterized by a N-ras gene mutation. , 1988, Leukemia.

[9]  J. Rhim,et al.  Activated H-ras oncogenes in human kidney tumors. , 1988, Cancer research.

[10]  Y. Nakamura,et al.  Genetic alterations during colorectal-tumor development. , 1988, The New England journal of medicine.

[11]  Collins Sj.  Direct sequencing of amplified genomic fragments documents N-ras point mutations in myeloid leukemia. , 1988 .

[12]  Irving S. Sigal,et al.  Cloning of bovine GAP and its interaction with oncogenic ras p21 , 1988, Nature.

[13]  J. Jiricny,et al.  Relapse cell population differs from acute onset clone as shown by absence of the initially activated N-ras oncogene in a patient with acute myelomonocytic leukemia. , 1988, Blood.

[14]  G. Riou,et al.  Somatic deletions and mutations of c-Ha-ras gene in human cervical cancers. , 1988, Oncogene.

[15]  G. Fleuren,et al.  KRAS codon 12 mutations occur very frequently in pancreatic adenocarcinomas. , 1988, Nucleic acids research.

[16]  F. Wyllie,et al.  Activated ras oncogenes in human thyroid cancers. , 1988, Cancer research.

[17]  F. McCormick,et al.  RAS mutations in myelodysplasia detected by amplification, oligonucleotide hybridization, and transformation. , 1988, Leukemia.

[18]  G. Mufti,et al.  Loss of ras oncogene mutation in a myelodysplastic syndrome after low-dose cytarabine therapy. , 1988, The New England journal of medicine.

[19]  D. Shibata,et al.  Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes , 1988, Cell.

[20]  J. Bos,et al.  The ras gene family and human carcinogenesis. , 1988, Mutation research.

[21]  M. D. Topal.  DNA repair, oncogenes and carcinogenesis. , 1988, Carcinogenesis.

[22]  D. Lowy,et al.  Guanosine triphosphatase activating protein (GAP) interacts with the p21 ras effector binding domain. , 1988, Science.

[23]  C. Marshall,et al.  The cytoplasmic protein GAP is implicated as the target for regulation by the ras gene product , 1988, Nature.

[24]  C. Bartram,et al.  Point mutation of the ras protooncogenes and chromosome aberrations in acute nonlymphocytic leukemia and preleukemia related to therapy with alkylating agents. , 1988, Cancer research.

[25]  B. Caillou,et al.  Detection of activated ras oncogenes in human thyroid carcinomas. , 1988, Oncogene.

[26]  B. Hjelle,et al.  Transforming genes in chronic myelogenous leukemia. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[27]  D. Birnbaum,et al.  Detection of a low frequency of activated ras genes in human melanomas using a tumorigenicity assay. , 1988, Cancer research.

[28]  J. J. Steinberg,et al.  H-ras activation in benign and self-regressing skin tumors (keratoacanthomas) in both humans and an animal model system , 1988, Molecular and cellular biology.

[29]  J. L. Bos,et al.  ras oncogene activation in human ovarian carcinoma. , 1988, Oncogene.

[30]  A. Gratwohl,et al.  Mutation analysis of the N‐ras proto‐oncogene in active and remission phase of human acute leukemias , 1988, International journal of cancer.

[31]  N. Ohuchi,et al.  Frequent overexpression, but not activation by point mutation, of ras genes in primary human gastric cancers. , 1987, Gastroenterology.

[32]  C. Bartram,et al.  RAS gene mutations in acute and chronic myelocytic leukemias, chronic myeloproliferative disorders, and myelodysplastic syndromes. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[33]  S. Hirohashi,et al.  Driven by the same Ig enhancer and SV40 T promoter ras induced lung adenomatous tumors, myc induced pre‐B cell lymphomas and SV40 large T gene a variety of tumors in transgenic mice. , 1987, The EMBO journal.

[34]  F. Hecht,et al.  Mutations of the Kirsten-ras proto-oncogene in human preleukaemia , 1987, Nature.

[35]  F. McCormick,et al.  A cytoplasmic protein stimulates normal N-ras p21 GTPase, but does not affect oncogenic mutants. , 1987, Science.

[36]  B. Vogelstein,et al.  Clonal analysis of human colorectal tumors. , 1987, Science.

[37]  S. Rodenhuis,et al.  Mutational activation of the K-ras oncogene. A possible pathogenetic factor in adenocarcinoma of the lung. , 1987, The New England journal of medicine.

[38]  D. Spandidos.  Oncogene activation in malignant transformation: a study of H-ras in human breast cancer. , 1987, Anticancer research.

[39]  H. Hirai,et al.  Highly frequent detection of transforming genes in acute leukemias by transfection using in vivo selection assays. , 1987, Biochemical and biophysical research communications.

[40]  S. H. Rider,et al.  Chromosome 5 allele loss in human colorectal carcinomas , 1987, Nature.

[41]  M. Santoro,et al.  A new oncogene in human thyroid papillary carcinomas and their lymph-nodal metastases , 1987, Nature.

[42]  G. Mcmahon,et al.  Characterization of c-Ki-ras oncogene alleles by direct sequencing of enzymatically amplified DNA from carcinogen-induced tumors. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[43]  H. Mano,et al.  A point mutation at codon 13 of the N-ras oncogene in myelodysplastic syndrome , 1987, Nature.

[44]  M. Melamed,et al.  Expression of p21ras in normal and malignant human tissues: lack of association with proliferation and malignancy. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[45]  A. Pellicer,et al.  Mutational activation of oncogenes in animal model systems of carcinogenesis. , 1987, Mutation research.

[46]  J. L. Bos,et al.  Mutations in N-ras predominate in acute myeloid leukemia. , 1987, Blood.

[47]  R. Palmiter,et al.  Pancreatic neoplasia induced by ras expression in acinar cells of transgenic mice , 1987, Cell.

[48]  E. Scolnick,et al.  Identification of effector residues and a neutralizing epitope of Ha-ras-encoded p21. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[49]  T. Sugimura,et al.  Transforming gene from human stomach cancers and a noncancerous portion of stomach mucosa. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[50]  R. Weinberg,et al.  Behavior of myc and ras oncogenes in transformation of rat embryo fibroblasts , 1986, Molecular and cellular biology.

[51]  A. Ogura,et al.  Sarcoma viruses carrying ras oncogenes induce differentiation-associated properties in a neuronal cell line , 1985, Nature.

[52]  R. Weinberg,et al.  Specific growth response of ras-transformed embryo fibroblasts to tumour promoters , 1985, Nature.

[53]  E. Winter,et al.  A method to detect and characterize point mutations in transcribed genes: amplification and overexpression of the mutant c-Ki-ras allele in human tumor cells. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[54]  D. Bar-Sagi,et al.  Microinjection of the ras oncogene protein into PC12 cells induces morphological differentiation , 1985, Cell.

[55]  C. Marshall,et al.  Amino-acid substitutions at codon 13 of the N-ras oncogene in human acute myeloid leukaemia , 1985, Nature.

[56]  J. Rhim,et al.  Frequency of molecular alterations affecting ras protooncogenes in human urinary tract tumors. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[57]  J. Bos,et al.  Three different mutations in codon 61 of the human N-ras gene detected by synthetic oligonucleotide hybridization. , 1984, Nucleic acids research.

[58]  M. Wigler,et al.  New human transforming genes detected by a tumorigenicity assay , 1984, Molecular and cellular biology.

[59]  M. Kraus,et al.  A position 12-activated H-ras oncogene in all HS578T mammary carcinosarcoma cells but not normal mammary cells of the same patient. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[60]  D. Lowy,et al.  The p21 ras C-terminus is required for transformation and membrane association , 1984, Nature.

[61]  P. Fialkow,et al.  Evidence for a multistep pathogenesis of a myelodysplastic syndrome. , 1984, Blood.

[62]  L. Old,et al.  Transforming ras genes from human melanoma: a manifestation of tumour heterogeneity? , 1984, Nature.

[63]  J. Minna,et al.  The biology of non-small cell lung cancer. , 1983, Seminars in oncology.

[64]  C. Cooper,et al.  New method for detecting cellular transforming genes. , 1982, Science.

[65]  R. Weinberg,et al.  Isolation of a transforming sequence from a human bladder carcinoma cell line , 1982, Cell.

[66]  M. Wigler,et al.  Human-tumor-derived cell lines contain common and different transforming genes , 1981, Cell.

[67]  G. Cooper,et al.  Transforming activity of human tumor DNAs. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[68]  P. Nowell.  The clonal evolution of tumor cell populations. , 1976, Science.

[69]  W. Wolff,et al.  Definitive Treatment of “Malignant” Polyps of the Colon , 1975, Annals of surgery.

[70]  H. Heimpel,et al.  Clonal analysis of myelodysplastic syndromes: evidence of multipotent stem cell origin. , 1989, Blood.

[71]  J. Bos,et al.  Mechanisms of ras mutation in myelodysplastic syndrome. , 1989, Oncogene.

[72]  H. Mano,et al.  Relationship between an activated N-ras oncogene and chromosomal abnormality during leukemic progression from myelodysplastic syndrome. , 1988, Blood.

[73]  Visvanathan Kv,et al.  Preferential and novel activation of H-ras in human bladder carcinomas. , 1988 .

[74]  C. Marshall,et al.  ras gene activation in a minor proportion of the blast population in acute myeloid leukemia. , 1987, Oncogene.

[75]  Y. Cheng,et al.  Oncogenes in human primary hepatic cancer , 1986, Journal of cellular physiology. Supplement.

[76]  S. Rodenhuis,et al.  Absence of oncogene amplifications and occasional activation of N-ras in lymphoblastic leukemia of childhood. , 1986, Blood.

[77]  S. Srivastava,et al.  High frequency of N-ras activation in acute myelogenous leukemia. , 1986, Blood.

[78]  J. Bos,et al.  A dot-blot screening procedure for mutated ras oncogenes using synthetic oligodeoxynucleotides. , 1986, Gene.

[79]  G. Kitchingman,et al.  Isolation of activated ras transforming genes from two patients with Hodgkin's disease. , 1985, International journal of radiation oncology, biology, physics.

[80]  M. Barbacid,et al.  Direct mutagenesis of Ha-ras-1 oncogenes by N-nitroso-N-methylurea during initiation of mammary carcinogenesis in rats , 1985, Nature.

[81]  V. Devita,et al.  Cancer : Principles and Practice of Oncology , 1982 .