Mitochondrial Mutations in Adenoid Cystic Carcinoma of the Salivary Glands

Suhail K Mithani,Chunbo Shao,Marietta Tan,Joseph A Califano,Adel K El-Naggar,Patrick K Ha,Ian M Smith

doi:10.1371/journal.pone.0008493

Abstract

BackgroundThe MitoChip v2.0 resequencing array is an array-based technique allowing for accurate and complete sequencing of the mitochondrial genome. No studies have investigated mitochondrial mutation in salivary gland adenoid cystic carcinomas.MethodologyThe entire mitochondrial genome of 22 salivary gland adenoid cystic carcinomas (ACC) of salivary glands and matched leukocyte DNA was sequenced to determine the frequency and distribution of mitochondrial mutations in ACC tumors.Principal FindingsSeventeen of 22 ACCs (77%) carried mitochondrial mutations, ranging in number from 1 to 37 mutations. A disproportionate number of mutations occurred in the D-loop. Twelve of 17 tumors (70.6%) carried mutations resulting in amino acid changes of translated proteins. Nine of 17 tumors (52.9%) with a mutation carried an amino acid changing mutation in the nicotinamide adenine dinucleotide dehydrogenase (NADH) complex.Conclusions/SignificanceMitochondrial mutation is frequent in salivary ACCs. The high incidence of amino acid changing mutations implicates alterations in aerobic respiration in ACC carcinogenesis. D-loop mutations are of unclear significance, but may be associated with alterations in transcription or replication.

Highlights

Adenoid cystic carcinoma (ACC) of the salivary gland is a rare malignancy, comprising 1% of all head and neck tumors, 10% of all salivary gland masses, and 22% of all salivary gland malignancies
There are a number of newer trials in progress, but there have been no major breakthroughs in chemotherapy for ACC
Tumor samples were derived from 22 patients who underwent resection of primary or locally recurrent lesions, and one sample was derived from nodal disease at the time of initial resection of ACC

Summary

Introduction

Adenoid cystic carcinoma (ACC) of the salivary gland is a rare malignancy, comprising 1% of all head and neck tumors, 10% of all salivary gland masses, and 22% of all salivary gland malignancies. The clinical behavior of ACC is atypical with an almost 40% incidence of distant metastases despite adequate local control with surgery and external beam irradiation [1]. Other atypical clinical features of ACC include a variable survival in patients with metastatic disease in a site dependent fashion. Many types of combination chemotherapy and molecular therapy have been investigated for use in ACC. There are a number of newer trials in progress, but there have been no major breakthroughs in chemotherapy for ACC. No studies have investigated mitochondrial mutation in salivary gland adenoid cystic carcinomas

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