© 2002 by Oxford University Press
Journal of the National Cancer Institute, Vol. 94, No. 10, 777,
May 15, 2002
© 2002 Oxford University Press
CORRESPONDENCE |
RESPONSE: Re: Genetic Analysis of the 
-Tubulin Gene, TUBB, in Non-Small-Cell Lung Cancer
Affiliations of author: M. J. Kelley, Thoracic Oncology Program, Duke University Medical Center and Durham Veterans Affairs Hospital, Durham, NC.
Correspondence to: Michael J. Kelley, M.D., Hematology/Oncology (111G), 508 Fulton St., Durham, NC 27705 (e-mail: kelleym{at}duke.edu).
In their letter to the Journal, Monzo et al. mistakenly state that we did not include the base-binding region in our analysis of TUBB. We amplified and sequenced the entire coding region and adjacent splice sites from all four exons in tumor cell lines and from the entire exon 4 (including the base-binding region) in tumor samples. We replicated their analysis of the ribose- and phosphate-binding regions and provided evidence for nonspecific amplification resulting in the detection of artifactual sequence variants in these regions. We could not replicate their analysis for the base-binding region of exon 4 because of an error in the sequence of an oligonucleotide in their original publication. The absence of TUBB mutations in tumors and cell lines calls into question the finding of mutations in serum DNA, as reported by Rosell et al. (1).
ale et al. (2) summarize their published analysis of the TUBB gene in human tumor samples, cell lines, and normal samples from the great apes. Using primers independently designed to avoid amplification of non-TUBB sequences and denaturing high-pressure liquid chromatography (dHPLC), no sequence variants were found that resulted in an altered amino acid sequence. Tsurutani et al. (3) have also been unable to detect any mutations of TUBB in 42 lung cancer samples by sequence analysis of cDNA, a technique that also avoids amplification of non-TUBB sequences. Taken together with results from my laboratory (4), it is clear that mutation of TUBB in human lung cancer is a rare occurrence or does not occur at all.
Oncologists have long sought the ability to predict the variable clinical tumor responses observed after chemotherapy treatment. Unfortunately, our current understanding of the complex and multifactorial mechanisms of drug resistance is insufficient to direct selection of drugs for patients with lung cancer. As increasing numbers of candidate markers of drug resistance and other potential predictors of clinical outcome emerge from the tools of the biotechnology revolution, we will be obligated to select only those markers with compelling and confirmatory preclinical studies for further analysis in clinical trials.
REFERENCES
1 Rosell R, Monzo M, Sanchez J, O'Brate A, Nogales E, Guillot M, et al. Beta-tubulin mutations in circulating extracellular DNA of non-small-cell lung cancer (NSCLC) patients [abstract]. Proc ASCO 2000;19:1897.
2
Sale S, Sung R, Shen P, Yu K, Wang Y, Duran G, et al. Conservation of the class I beta-tubulin gene in human populations and lack of mutations in lung cancers and paclitaxel-resistant ovarian cancers. Mol Cancer Ther 2002;1:215–25.
3 Tsurutani J, Komiya T, Uejima H, Tada H, Syunichi N, Oka M, et al. Mutational analysis of the beta-tubulin gene in lung cancer. Lung Cancer 2002;35:11–6.[CrossRef][Medline]
4
Kelley MJ, Li S, Harpole DH. Genetic analysis of the beta-tubulin gene, TUBB, in non-small cell lung cancer. J Natl Cancer Inst 2001;93:1886–8.
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