title: Association between activated K-ras and c-erbB-2 oncogenes with "high-risk" and "low-risk" human papilloma virus types in preinvasive cervical lesions.
abstract: Clinical and epidemiological data have linked cervical cancer to the Human Papilloma Virus (HPV) infection. However, the presence of HPV infection alone is not enough to cause tumorigenesis, suggesting a role for additional host-cell genetic factors. The aim of the present work was to study the association of K-ras and c-erbB-2 mutations in cervical tissue samples with different grades of dysplasia and infected with HPV-6 ("low-risk" type) or HPV-16 and HPV-18 ("high-risk" types). Negative HPV-DNA samples were used as controls. The detection of K-ras and c-erbB-2 activation were performed by Artificial Refractory Mutation System (ARMS)-PCR and semiquantitative PCR, respectively. Statistical analysis showed a highly significant difference in K-ras codon 12 mutation frequency between high-risk and low-risk HPV-infected samples (p<0.05). On the other hand, amplification of the c-erbB-2 oncogene appeared associated to tissue samples infected with HPV-6 (p<0.003). Cervical carcinoma appears to arise from a series of well-characterized progressive histological changes, but the genetic alterations necessary for cervical tumorigenesis are not yet clear. These results raise the possibility for a role of certain proto-oncogenes and their activation in cervical neoplasia.
authors.affiliation: Centro de Investigaciones en Genética Básica y Aplicada (CIGEBA), Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, Calle 60 y 118 s/n, B1900AVW, La Plata, Argentina.
authors.forename: S A
authors.initials: SA
authors.lastname: Mourón
authors.forename: M C
authors.initials: MC
authors.lastname: Abba
authors.forename: A
authors.initials: A
authors.lastname: Güerci
authors.forename: M A
authors.initials: MA
authors.lastname: Gómez
authors.forename: F N
authors.initials: FN
authors.lastname: Dulout
authors.forename: C D
authors.initials: CD
authors.lastname: Golijow
mesh_terms: D000328:Adult; D002278:Carcinoma in Situ / Q000235:genetics / Q000473:pathology / Q000821:virology; D002584:Cervix Uteri / Q000166:cytology / Q000473:pathology / Q000821:virology; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D018734:Genes, erbB-2; D011905:Genes, ras; D016679:Genome, Viral; D006801:Humans; D027383:Papillomaviridae / Q000145:classification / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000150:complications / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction / Q000379:methods; D018570:Risk Assessment; D014412:Tumor Virus Infections / Q000150:complications / Q000235:genetics* / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000235:genetics* / Q000473:pathology / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology
chemical_list: D004279:DNA, Viral