Genomic instability and tumor-specific alterations in oral squamous cell carcinomas assessed by inter-(simple sequence repeat) PCR.
OBJECTIVE
Genomic instability plays a major role in the genesis and progression of tumors, and in the evolution of tumor heterogeneity. To determine the role of genomic instability in the genesis and progression of oral cancer, we assessed the extent of genomic alterations in oral squamous cell carcinomas (OSCCs).


METHODS
We used the recently developed inter-(simple sequence repeat) PCR technique to quantitate genomic instability using matched tumor and normal OSCC samples (n = 25). The inter-repeat region bands of similar molecular size observed to be altered in more than one case were sequenced and analyzed to identify probable OSSC-associated specific genetic lesions.


RESULTS
Of the four base-anchored, dinucleotide repeat-based primers used for the study, the most informative profile in OSCCs was generated by the (CA)(8)RG primer. Measurement of genomic instability index using the (CA)(8)RG primer revealed a high incidence of genomic instability in OSCCs. No significant correlation between the extent of alterations and stage or location of the tumor was observed. Sequencing analysis of the altered bands revealed gains/losses in several chromosomal regions. Of the matched tumor and corresponding normal tissue DNA studied, hitherto unreported losses were seen in 11p15 and 17q25 chromosomal regions. Sequencing of some of the tumor-specific altered regions indicated that they code for regions of UDP-GalNAc and hRAD 17 genes, which were lost (deleted) in oral cancer.


CONCLUSIONS
Our results indicate that the extent of genomic instability in OSCC is not correlated to the tumor stage or location. For the first time, we have shown that chromosomal alterations detected by inter-(simple sequence repeat) PCR could be correlated to genes associated with cancer development.
Viswanathan
Muthusamy
M
Cancer Biology Division, Center for Advanced Study in Functional Genomics, School of Biological Sciences, Madurai Kamaraj University, Madurai 625 021, India.
Sangiliyandi
Gurunathan
G
Vinod
Saladi S
SS
Mohanprasad
Bagavathi K C
BK
Shanmugam
Govindaswamy
G
D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000378:metabolism*; D010641:Phenotype; D016133:Polymerase Chain Reaction
D017931:DNA Primers