A review of chromosome 3q abnormalities in lung cancer.

Abstract

e21154 Background: With the refinement of genetic analytic techniques more detailed and precise information about 3q abnormalities has become available. The aim of this study was to review and summarize the literature about chromosome 3q in the pathogenesis, classification, treatment and prognosis of lung cancer. Methods: A MEDLINE search was conducted with the terms “lung cancer” and “3q”. Papers that described 3q abnormalities in the context of lung cancer were included in this review. Results: From 1990-2011, 61 papers were identified that described chromosome 3q changes in lung cancer. Initial studies showed 3q amplification in premalignant lesions, bronchial dysplasia, NSCLC and SCLC tumor tissue. Similar 3q amplifications were found in lung cancer cell lines at the 3q26-q28 region, including the gene for telomerase (hTR). Amplification of 3q segments were more prevalent in squamous (40 -100%) than in adenocarcinoma (6 - 25%) and in smokers than in non-smokers. However, malignant cells from pleural effusions of adenocarcinoma showed 3q gains in nearly 40% of cases. Genes located on 3q such as RAP2B, CLDN1 and TBL1XR1 were overexpressed in squamous carcinoma. High gain levels were also found at PIK3CA, EVI1 (3q26.2), LPP (3q27-28) and FHF-1 (3q28) gene loci. Also, 3q gains were associated with EGFR mutations in squamous carcinoma and TP53 mutations in adenocarcinoma. Prognostic importance of several chromosomal changes in lung cancer has also been examined. In one study, overexpression of eIF5A-2, located on 3q, was found to correlate with gene amplification, increased cell proliferation, local invasion, advanced T stage, and poor prognosis in stage I NSCLC [He, Int J Cancer, 2011]. Conclusions: Genetic abnormalities and changes in chromosome 3q have been increasingly well characterized with specific genes identified. Differential expression in various histological types of NSCLC indicates that these genes may contribute to the pathogenetic pathway in squamous carcinoma, and also in locally advanced adenocarcinoma with pleural effusions. These genes have also been shown to be prognostically important. With these promising results, further identification of specific 3q gene products may lead to the development of novel therapeutic targets in lung cancer.