Determination of the use of CGH array to detect chromosomal instability (CIN)

3740 Background: It is suggested that the presence of a TP53 mutation and a microsatellite stable (MSS) phenotype are associated with chromosomal instability (CIN). Further CIN phenotype appears to be associated with shorter survival (a more aggressive tumor type) compared to the microsatellite instability (MIN) phenotype. Whereas the MIN phenotype can readily be assessed by PCR with (a) set(s) of consensus markers, assessing the CIN phenotype needs much more laborious methods such as microscopic analysis of metaphases or extensive analysis of loss of heterozygosity. As an alternative we have explored the use of a subtelomeric comparative genomic hybridization (CGH) array to detect presence of chromosomal instability (CIN). Methods: Formalin-fixed paraffin-embedded (FFPE) tumor (and normal) specimens were available from patients with stage III colon cancer adjuvantly treated with 5-fluorouracil-based chemotherapy. Tumor vs. matched normal DNA from 8 stage III colon specimens, selected for presence of TP53 mutation and a microsatellite stable phenotype, were hybridized on subtelomeric CGH arrays (n= 464 BACs). Results: Preliminary results show that 5 out of 8 analyzed MSS colon tumors with a TP53 mutation gave interpretable results. All 5 interpretable tumors showed at least 3 aberrations. Chromosomal gains on 20q were found in 4/5 specimens, on 13q in 3/5 specimens and on 8q in 2/5specimens. Conclusion: All five tumors that gave interpretable results show chromosomal abnormalities of at least 3 chromosome arms. Because of our use of subtelomeric arrays, we cannot detect interstitial gains or losses. Therefore, our results most likely represent an underestimation of aberrations present. We conclude that in principle subtelomeric CGH arrays can be used to determine a CIN phenotype. No significant financial relationships to disclose.