Specific rearrangements of human chromosome 3 have been characteristically associated with malignant and developmental disorders. Deletion of the chromosome 3p14-21 region is the constant cytogenetic feature in spontaneous carcinoma of the kidney and the same region is involved in hereditary renal carcinoma due to a 3;8 translocation. This region is also part of a larger deletion (3p14-23) characteristically associated with small cell carcinoma of the lung, the seventh most common form of cancer in the United States and a disease which is doubling in incidence every decade. Chromosome 3p14.2 is also the location of the most common constitutive fragile site which may be involved in the pathogenesis of some of these rearrangements. We propose to characterize the chromosome 3p14-21 region, especially the 3p14.2-3p21.1 area which is bounded by two biologically important translocations, and which is common to the renal and small cell carcinoma deletions. These are the hereditary renal cell translocation, t(3;8)(p14.2;q24.1) and the familial Grieg Polysyndactyly craniofacial anomalies 3;7 translocation, t(3;7)(p21.1;p13). We will construct a physical linkage map of this region using a combination of somatic cell hybrids which define and span this region, DNA sequences from a flow sorted chromosome 3 library, and pulsed-field electrophoresis. We propose to define at the molecular level a region which is consistently altered in renal and small cell lung cancer, and to isolate the breakpoint in the hereditary renal carcinoma 3;8 translocation. These studies should facilitate the isolation of a critical gene(s) involved in the pathogenesis of these diseases, and should also contribute to the mapping and sequencing of the human genome
