Dr Manfred Schartl, Gene Center, Max-Planck-Institute
for Biochemistry, Martinsried, Fed. Rep. Germany

In the May issue (Nr. 9) of the Pigment Cell Research Bulletin a commentary by Zechel C, Schleenbecker G, Anders A and Anders F and by the editor was published stating that the work of our group (Wittbrodt et al, Nature 341:415-421,1989), dealt with the same subject, that we also found an EGF (receptor) related Tu-gene. but that we did not quote the previously published work by Zechel et al (Oncogene 3:605-617,1988). This implicates : 1) our manuscript and that of Zechel et al contain the comparable experimental work and results; 2) the work of Zechel et al is the first report of its kind; 3) our group does not quote correctly important work in the same area; 4: the group of Prof. Dr. Anders, Giessen, has first reported that the long sought Tu-gene of Xiphophorus is an EGF-receptor like gene.

My collaborators and I disagree to that. Our reasons for that are:

1 The manuscript of the Anders group describes a v-erb B related sequence, which cosegregates with certain sex-chromosomes that harbour a Tu-locus, cloning of this sequence, a partial nucleotide sequence (approx. 500 bp in total. coding 250 bp) and its expression in two established cell lines.

Our manuscript demonstrates that such a sequence is not only closely physically linked to Tu, but the critical constituent of this locus. We describe cloning and genomic organization of more than 45 kb of the corresponding loci, show its simultaneous presence as proto-oncogene and oncogene in the genome of susceptible fish, isolation and sequence of a full length c-DNA (approx. 4000 bp thereby proving hat it is a function al gene), show that this gene is a novel putative receptor tyrosine kinase, its differential expression during embryonic development and its strongly enhanced and aberrant expression in 12 different samples from melanoma biopsies. Central and most important for our paper is the analysis of a loss of function mutant, which we showed to be due to the insertional inactivation of the gene that we have described, being so far the single experimental proof that this novel receptor tyrosine kinase is indeed the melanoma inducing gene encoded by the Tu-locus.

We are confident that the manuscript of Zechel et al and our manuscript do not contain comparable work.

2 The cloning, the linkage and extended expression data not only in cell lines but also in a variety of normal tissues and in melanoma of a v-erb B related sequence was published by our group in a total of four manuscripts all of which appeared prior to the paper by Zechel et al (Dec. 88). These are : Mäueler et al, Oncogene 2:421-430, 1988; Schartl, Genetics 119:679-695. 1988; Adam et al, Nucl Acid Res 16:7212, 1989, Mäueler et al, Oncogene 3:113-122, 1988. None of these have been quoted in the paper by Zechel et al.

3 In our article when we were referring to some earlier work that has led us to the isolation of Tu, we made use of our own original data rather than using the confirmatory work of others. If there is something in our article which may look related to the work of Zechel et al to somebody from other fields in research, this may be contained on page 415 in the last paragraph.
We would, however, like to stress that our experiment described there is a linkage analysis of the cloned marker sequence and one specific Tu-allele (Tu-Sd) and we cannot find such experiment in the paper of Zechel et al.

4 Concerning the claim that the Tu-gene is a EGF-receptor (or v-erb B) related gene we would like to add that in the paper by Zechel et al the authors state explicitely a) that the v-erb B related sequences "are located between the respective pterinophore locus ... and the Tu complexes ..." b) that the v-erb B related sequences "do not mediate the process of neoplastic transformation itself, but are rather involved in other processes such as determination of the target cells ..." c) "The biological nature of the formally defined tumor gene Tu still remains unknown".

On the contrary, our group has always suggested (e.g. see our papers from 1988) and finally conclusively proven that the v-erb B related sequence which we have designated Xmrk is the Tu gene (see Wittbrodt et al).