A human c-erbA oncogene homologue is closely proximal to the chromosome 17 breakpoint in acute promyelocytic leukemia.

TLDR

The proximity of c‑erbA sequences to breakpoints in two leukemias suggests a potential role for this oncogene homologue in tumor development. The authors screened a human cDNA library for erbA homologues, identified clone cHerbA‑1, and used it in Southern blot and in situ hybridization to map the c‑erbA locus to chromosome 17q21‑q24 in normal and APL cells, and further confirmed its absence on the 21q+ chromosome in a t(17;21) leukemia. The study localized c‑erbA to chromosome 17q21‑q24 and showed it remains on the 17q‑ chromosome in APL cells and is absent from the 21q+ chromosome in a t(17;21) leukemia, supporting its assignment to the 17q21‑q22 region.

Abstract

A human cDNA library was screened for sequences homologous to the erbA gene of avian erythroblastosis virus (AEV). One such clone, cHerbA-1, was used to map the chromosomal location of highly homologous human sequences that were found to be present on chromosome 17 as judged by Southern blot screening of a panel of mouse-human hybrid cell lines segregating human chromosomes. cHerbA-1 was hybridized in situ to metaphase chromosomes from a normal male subject and from a female patient with an acute promyelocytic leukemia (APL) having the typical t(15;17) translocation. The results localized the cellular c-erbA sequences on chromosome 17 to the q21-q24 region of normal chromosomes and indicated that the c-erbA sequences remained on the 17q- chromosome in the APL cells, suggesting that they could be assigned to the 17(q21-q22) region. For additional data, we hybridized human neoplastic cells derived from a poorly differentiated acute leukemia carrying a t(17;21) translocation with thymidine kinase (TK)-deficient LMTK- mouse cells. A resulting hybrid, containing only the 21q+ chromosome, did not have human c-erbA sequences. Since the breakpoint on 17q in this translocation was similar to that in the APL t(15;17) translocation, this supported the assignment of c-erbA to the q21-q22 region of chromosome 17. The apparent close proximity of the c-erbA sequences to the chromosomal breakpoints in these two leukemias suggests a possible role for this oncogene homologue in the development of these neoplasms.