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About the Authors:
Zhihong Shan
Affiliation: Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, United States of America
Abbas Shakoori
Affiliation: Advanced Genome Technology Center, Mayo Clinic and Foundation, Rochester, Minnesota, United States of America
Sohrab Bodaghi
Affiliation: Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, United States of America
Paul Goldsmith
Affiliation: Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, United States of America
Jen Jin
Affiliation: Advanced Genome Technology Center, Mayo Clinic and Foundation, Rochester, Minnesota, United States of America
Jonathan S. Wiest
* E-mail: [email protected]
Affiliation: Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, United States of America
Introduction
Lung cancer is the most common form of cancer mortality in men and women in the world with an estimated 226,160 new cases and 160,340 deaths occurring in the United States in 2012 [1]. Lung cancer develops through a multistage process involving a variety of genetic and epigenetic changes in dominant oncogenes and tumor suppressor genes (TSGs) [2]. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer subtypes with small cell lung cancer accounting for the remaining 15% [3], NSCLC is further subdivided into adenocarcinoma (39%), squamous cell carcinoma (21%), large cell carcinoma adenocarcinoma (3%), and uncommon types and combined types comprising the remaining 22% [3].
Alteration of chromosome 9p is implicated in a variety of tumor types including melanoma, non small cell lung carcinoma, breast cancer, leukemia, and hepatocellular carcinoma, clear cell renal cell carcinomas and gastrointestinal stromal tumors through chromosomal inversions, translocations, loss of heterozygosity (LOH) and homozygous deletion (HD). Genetic alterations of chromosome 9p occur early and frequently in lung cancer. These data suggest chromosome 9p contains a tumor suppressor locus (loci) critical in the development of several tumor types including lung [4]–[17]. Two candidate tumor suppressor loci were identified in the chromosome 9p21 region. One locus is p16/CDKN2A, which encodes the p16 and p14ARF proteins. The other locus is p15/CDKN2B encoding the p15 protein [7], [18], [19]. Since p16/CDKN2A is frequently inactivated genetically or epigenetically in cancer cells, the p16/CDKN2A locus is suspected to be a major tumor suppressor gene...