Mitochondrial Mutations Are a Late Event in the Progression of Head and Neck Squamous Cell Cancer

Abstract

Purpose:To determine the timing of mitochondrial mutations in the progression of head and neck squamous cell carcinoma. Experimental Design:Twenty-three mitochondrial mutations were identified in 12 tumors using a high-throughput mitochondrial sequencing array. Areas of adjacent dysplastic and normal epithelium adjacent to tumors were sequenced using conventional methods for the presence of mutations that occurred in the corresponding tumor. Results: Two of 23 (8.7%) tumor mitochondrial mutations (2 of 12 tumors) were present in both the areas of adjacent dysplasia and normal epithelium. Five of 23 (21.7%) tumor mitochondrial mutations (4 of 12 tumors) were present in areas of adjacent dysplasia. Eleven of 12 tumors contained nonsynonymous mutations that resulted in protein coding alterations. A significant difference (P < 0.01, m 2 ) was found in the incidence of mitochondrial mutation that occurred after development of cancer compared with adjacent areas dysplasia and normal epithelium. Conclusions: The majority of mitochondrial mutations occur during or after the transition of preneoplastic epithelium to cancer in head and neck squamous cell carcinoma, indicating that these are a late event in head and neck carcinogenesis.

MtDNA As a Cancer Marker: A Finally Closed Chapter?

“…Their occurrence seems to be rather late e.g. in head and neck cancers [84]. For BC no comparable data of significant series of patients are available, which would allow a precise analysis of this aspect.…”

D-loop somatic mutations and ∼5 kb “common” deletion in mitochondrial DNA: important molecular markers to distinguish oral precancer and cancer

“…Mutations in D-loop region and ∼5 kb deletion in mtDNA have also been implicated to increase ROS production, which may be driving force for tumorigenesis [18][19][20][21][22]. Few reports suggested an increase in D-loop somatic mutations in cancer tissue [23,24], while some studies found ∼5 kb deletion to be more prevalent in precancerous lesion or adjacent non-cancerous tissues than in malignant cancerous tissue [25][26][27]. But comparative study of mtDNA contents and mutations in oral cancer and precancer tissues are very few.…”

A Disturbance in the Force—Mitochondrial Mutations in Squamous Cell Carcinoma of the Head and Neck

“…1). Over a decade before Lucas was born, Otto Warburg, in 1931, observed that cancer cells consume oxygen via mitochondrial oxidative phosphorylation at much higher rates than normal cells and hypothesized that cancer was actually the result of mitochondrial defects (2).…”

“…A gene array chip is now commercially available that can sequence the mitochondrial genome in just 48 h. A derivative of this relative facility in sequencing is the creation of a public database of mtDNA population variation in human evolution and disease, the MITOMAP. 1 This internet-based tool provides the user-detailed information on mtDNA sequence, function, polymorphisms, haplogroups, and mutations-both germ line and somatic associated with disease states.…”