The murine Ick gene is closely related to a family of cellular protooncogenes and encodes a lymphocytespecific, membrane-associated protein tyrosine kinase. We and others have demonstrated that the Ick gene is rearranged and overexpressed in the murine lymphoma LSTRA, most likely as a result of the insertion of Moloney murine leukemia virus DNA immediately adjacent to the gene. We now report that the Ick gene is located at the distal end of murine chromosome 4 and on human chromosome 1 at position lp32-35 near a site of frequent structural abnormalities in human lymphomas and neuroblastomas. These results raise the possibility that structural alteration of the ick gene through chromosomal rearrangement may contribute to transformation in human malignant disease.At least twelve genes encoding protein tyrosine kinases have been implicated in neoplastic transformation in mammalian cells (1, 2). Broadly speaking, characterized protein tyrosine kinase genes can be divided into two subfamilies. The first -encodes a group of cell-surface receptors that mediate mitogenesis. Ligands for these receptors are in three cases known, the epidermal growth factor (EGF) receptor (3), the insulin receptor (4), and the colony-stimulating factor 1 (CSF-1) receptor (5), while two other members of this subfamily encode receptor structures for which ligands are at present unidentified, neu (6, 7) and trk (8). A second subfamily of protein tyrosine kinase genes encodes a group of proteins that are typically membrane-associated but which lack recognizable transmembrane domains, for example abl, fgr, src, and lck** (1, 2, 9, 10). The protein tyrosine kinase oncogenes were originally identified as components of acutely transforming retroviruses or through transformation of cultured fibroblasts via transfection of tumor DNA (1, 2). In at least one case, the t(9;22) translocation of human chronic myelogenous leukemia, activation of a protein tyrosine kinase protooncogene (abi) results from a spontaneous chromosomal rearrangement (11,12). Thus protein tyrosine kinases may in some cases be involved in the specific chromosomal abnormalities frequently detected in human and murine neoplasia.The murine Ick gene encodes a lymphocyte-specific, membrane-associated protein tyrosine kinase of unknown function. We and others have demonstrated that this gene is rearranged and overexpressed in the murine lymphoma LSTRA, most likely as a result of insertion of Moloney murine leukemia virus sequences immediately upstream of the gene (9, 10). We now report that the Ick gene is located on human chromosome 1 at position 1p32-35 in a site of frequent structural abnormalities in human lymphomas and neuroblastomas. These results suggest that structural alteration of the lck gene through chromosomal rearrangement may occasionally contribute to transformation in human malignant disease. (14). Hybridization of the lck probe to mitotic chromosomes was performed by a modification of the method of Harper and Saunders (15). Briefly, chromosome slide preparatio...