Expression of the HMGA2-LPP fusion transcript in only 1 of 61 karyotypically normal pulmonary chondroid hamartomas

The HMGA2 gene has been found to be rearranged in a variety of benign solid tumors. However, in all tumor entities where aberrations of the corresponding chromosomal region have been found, a large percentage of tumors do not show any detectable cytogenetic deviation. Thus, the question arises whether or not in some of these cases, small subpopulations of tumor cells characterized by HMGA2 rearrangements exist. The existence of these populations would strongly suggest a secondary nature of the chromosomal aberrations. Herein, we have addressed this question by RT-PCR analyses of the HMGA2-LPP fusion resulting from t(3;12)(q27∼q28;q14∼q15) in a series of 61 pulmonary chondroid hamartomas (PCH) with an apparently normal karyotype. As a result, the HMGA2-LPP fusion transcript was amplified in only one of 61 PCH with a normal karyotype. In this case, fluorescence in situ hybridization analysis revealed a hidden chromosomal aberration. The absence of the HMGA2-LPP fusion in small populations of tumors with a normal karyotype suggests the primary nature of chromosomal rearrangements in the development of PCH affected by those aberrations.