Genetic Analysis of the -Tubulin Gene, TUBB, in Non-Small-Cell Lung Cancer

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Abstract
Tubulin, the cellular target for the taxane chemotherapeutic agents, is composed of αβ heterodimers. There are at least six human genes encoding different tubulin β subunits (1). In most epithelial tumor cells, the most highly expressed isoform of β-tubulin is β5, which is encoded by the TUBB gene, also referred to as M40 (2). Chinese hamster ovary cells (3) and an ovarian tumor cell line (4) adapted for growth in vitro in the presence of the taxane paclitaxel have been found to have mutations in TUBB. Monzó et al. (5) reported TUBB mutations in 16 (33%) of 49 tumor samples from previously untreated patients with advanced non-small-cell lung cancer (NSCLC). All of the mutations, except two, were located in exon 4, which encodes more than half of the β-tubulin protein and includes the adenosine triphosphate-binding site composed of the ribose-, phosphate-, and base-binding regions. There was also a statistically significant association between the presence of TUBB mutations and both poor treatment response to paclitaxel-containing chemotherapy and shortened overall survival (5). These associations led to the proposal to use the presence of TUBB mutations as a basis for selecting initial chemotherapy for patients with advanced NSCLC (6).