Novel regions of amplification on 8q distinct from the MYC locus and frequently altered in oral dysplasia and cancer.
Genetic studies aimed at identifying key alterations in oral cancers have focused on analysis of tumors, with few such studies using early oral premalignant lesions (OPLs) because of limitations in both sample availability and size. In this study, we used a randomly amplified polymorphic DNA (RAPD)-PCR approach to fingerprint DNA from microdissected normal and dysplastic cells and identified two recurrent genetic alterations on the long arm of chromosome 8 in OPLs, one mapping to 8q22 and the other to 8q24 near the MYC locus. We constructed a high-resolution bacterial artificial chromosome (BAC) comparative genomic hybridization array consisting of 166 overlapping BAC clones that spans about 52 Mbp, from 8q21 to 8q24. Hybridization of DNA from microdissected oral tumors to the array revealed alteration at 8q24, with amplification of the BAC containing MYC. Strikingly, at least two other novel regions of amplification at 8q22 were identified. Microsatellite analysis of 93 oral dysplasias and tumors confirmed the presence of one of the alterations at 8q22. Loss of heterozygosity (LOH) at D8S1830, mapping within one of the regions of amplification, was observed in high frequency in both OPLs and tumors. Of the 37 cases with LOH at D8S1830, 23 (62%) showed retention at D8S1793, which maps 1.6 Mbp centromeric to MYC. This is further support for the alteration at 8q22 being distinct from MYC. These data raise the possibility of additional oncogenes on 8q near the MYC locus that are potentially involved in OPL disease progression.
Garnis
Cathie
C
British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada. garnis@bccancer.bc.ca
Coe
Bradley P
BP
Ishkanian
Adrian
A
Zhang
Lewei
L
Rosin
Miriam P
MP
Lam
Wan L
WL
D014408:Biomarkers, Tumor / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D005784:Gene Amplification / Q000235:genetics*; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology; D011230:Precancerous Conditions / Q000235:genetics*
D014408:Biomarkers, Tumor