Intratumor heterogeneity of K-ras2 mutations in colorectal adenocarcinomas: association with degree of DNA aneuploidy.

摘要: Detailed information about intratumor K-ras2 mutations in colorectal adenocarcinomas and a possible association with DNA content heterogeneity is still lacking. diploid aneuploid subclones, detected among multiple histologically selected primary sectors (57 superficial 40 deep) 9 lymph node metastases, were flow cytometrically sorted separately submitted to codons 12-13 mutation spectrum analysis. aneuploidy was absent 20 near distant mucosa sites present 7/9 metastases 17/19 tumors (90%). Primary multiclonality approximately 50%. Degree of (DNA Index) distribution nonrandom showed peaks at approximate mean Index values 1.2, 1.5, 1.8. 0/20 cases, 2/9 9/19 (47%). No more than one type per tumor detected. Intratumor homogeneous 6 heterogeneous 3 cases. Homogeneous associated near-diploid aneuploidy. strongly the region (83%) almost (5%) near-triploid subclones (P = 0.0001). indicates that sampling may be critical step suggests activation late event subgroup tumors. Our data also suggest existence an early process carcinogenesis favors both Onset appears, instead, independent from activation.