Mitochondrial D-loop polymorphism in tubular adenomas and serrated polyps of colorectal lesions

Abstract

Colorectal cancer is a heterogeneous disorder than arises via multiple distinct pathways, from tubular adenomas (TAs) and serrated polyps (SPs), which are clinically, morphologically, and molecularly different. We examined mitochondrial D-loop polymorphism in colorectal precancerous lesions, including TAs and SPs. DNA was isolated from paired normal and tumoral tissues in 78 TAs and 34 SPs. Mitochondrial D-loop polymorphism (D146, D150, D152, D310, and D514), KRAS and BRAF mutations, and microsatellite instability (MSI) were analyzed by direct sequencing and pyrosequencing. D146, D310, and D514 were polymorphic in these patients and their distributions were significantly different between TAs and SPs. D146 and D310 polymorphism was associated not with KRAS and BRAF mutations, but with MSI and other mitochondrial polymorphism each other. Our data suggest that mitochondrial D-loop polymorphism may play an important role in development of colorectal precancerous lesions and contribute to regulate their progression to TAs or SPs.