Similar regions of human chromosome 3 are eliminated from or retained in human/human and human/mouse microcell hybrids during tumor growth in severe combined immunodeficient (SCID) mice

By passaging microcell hybrids (MCHs) containing human chromosome 3 (chr3) on A9 mouse fibrosarcoma background through severe combined immunodeficient (SCID) mice (elimination test), we have previously defined a 1-Mb-long com mon eliminated region 1 (CER1) at 3p21.3, a second eliminated region (ER2) at 3p21,1-p14 and a common retained region (CRR) at 3q26-qter. In the prese nt work, chr3 was transferred by microcell fusion into the human nonpapilla ry renal cell carcinoma line KH39 that contained uniparentally disomic chr3 . Four MCHs were generated. Compared with KH39, they developed fewer and sm aller tumors, which grew after longer latency periods in SCID mice. The tum ors were analyzed in comparison with corresponding MCHs by chr3 arm-specifi c painting, 19 fluorescent in situ hybridization (FISH) probes, and 27 poly morphic markers. Three MCHs that maintained the intact exogenous chr3 in vi tro lost one 3p copy in all 11 tumors. Seven of 11 tumors lost the exogenou s 3p, whereas four tumors contained mixed cell populations that lacked eith er the exogenous or one endogenous KH39 derived 3p. In one MCH the exogenou s chr3 showed deletions within CER1 and ER2 already in vitro. It remained e ssentially unchanged in 8/9 derived tumors. The third, exogenous copy of th e 3q26-q27 region (part of CRR) was retained in 16/20 tumors. It can be con cluded that the human/human MCH-based elimination test identifies similar e liminated and retained regions on chr3 as the human/murine MCH-based test.