Affiliations: Department of Pathology, Aberdeen Royal Infirmary,
Link Building, Foresterhill, Aberdeen, AB25 2ZN, UK | Department of Biochemistry and Molecular Biology,
University of Southern California, Keck School of Medicine, Norris
Comprehensive Cancer Center, 1441 Eastlake Ave. Rm NOR6420, Los Angeles, CA
90089-9176, USA | Department of Surgery, University of Southern
California, Keck School of Medicine, Norris Comprehensive Cancer Center, 1441
Eastlake Ave. Rm NOR6420, Los Angeles, CA 90089-9176, USA
Note: [] Corresponding author: Ite A. Laird-Offringa, Ph.D., USC/Norris
Cancer Center, 1441 Eastlake Ave. Rm NOR6420, Los Angeles, CA 90089-9176, USA.
Tel.: +1 323 865 0655; Fax: +1 323 865 0158; E-mail: [email protected]
Abstract: Lung cancer, caused by smoking in ∼87% of
cases, is the leading cause of cancer death in the United States and Western
Europe. Adenocarcinoma is now the most common type of lung cancer in men and
women in the United States, and the histological subtype most frequently seen
in never-smokers and former smokers. The increasing frequency of
adenocarcinoma, which occurs more peripherally in the lung, is thought to be at
least partially related to modifications in cigarette manufacturing that have
led to a change in the depth of smoke inhalation. The rising incidence of lung
adenocarcinoma and its lethal nature underline the importance of understanding
the development and progression of this disease. Alterations in DNA methylation
are recognized as key epigenetic changes in cancer, contributing to chromosomal
instability through global hypomethylation, and aberrant gene expression
through alterations in the methylation levels at promoter CpG islands. The
identification of sequential changes in DNA methylation during progression and
metastasis of lung adenocarcinoma, and the elucidation of their interplay with
genetic changes, will broaden our molecular understanding of this disease,
providing insights that may be applicable to the development of targeted drugs,
as well as powerful markers for early detection and patient classification.
Keywords: AAH, adenocarcinoma, BAC, CpG island, DNA methylation, hypermethylation, hypomethylation
