Department of Neuroscience, Karolinska Institute, S-17177 Stockholm, Sweden.
Cold Spring Harb Perspect Biol. 2013 Feb 1;5(2):a009134. doi: 10.1101/cshperspect.a009134.
The identification of the ret oncogene by Masahide Takahashi and Geoffrey Cooper in 1985 was both serendipitous and paradigmatic ( Takahashi et al. 1985). By transfecting total DNA from a human lymphoma into mouse NIH3T3 cells, they obtained one clone, which in secondary transformants yielded more than 100-fold improvement in transformation efficiency. Subsequent investigations revealed that the ret oncogene was not present as such in the primary lymphoma, but was derived by DNA rearrangement during transfection from normal human sequences of the ret locus. At the time, activation by DNA rearrangement had not been previously described for a transforming gene with the NIH3T3 transfection assay. The discovery of ret opened a field of study that has had a profound impact in cancer research, developmental biology, and neuroscience, and that continues to yield surprises and important insights to this day.
1985 年，Masahide Takahashi 和 Geoffrey Cooper 偶然发现了 ret 癌基因，这一发现具有开创性意义（Takahashi 等人，1985 年）。他们通过将人类淋巴瘤的总 DNA 转染到小鼠 NIH3T3 细胞中，获得了一个克隆，在次级转化体中，转化效率提高了 100 多倍。随后的研究表明，原代淋巴瘤中并不存在 ret 癌基因，而是在转染过程中通过 DNA 重排从 ret 基因座的正常人类序列中衍生而来。当时，在 NIH3T3 转染实验中，DNA 重排激活转化基因的情况以前尚未被描述过。ret 的发现开辟了一个研究领域，对癌症研究、发育生物学和神经科学产生了深远的影响，并一直持续到今天，不断带来惊喜和重要的见解。
