HMGI-C rearrangements as the molecular basis for the majority of pulmonary chondroid hamartomas: a survey of 30 tumors.
Pulmonary chondroid hamartomas (PCH) are benign tumors of the lung characterized by a more or less high degree of mesenchymal metaplasia. In our series we investigated 30 PCH by a combination of cytogenetic and molecular methods. 18 tumors (60%) had cytogenetically detectable aberrations involving either 12q14-15 or 6p21 with a clear predominance of chromosomal abnormalities involving 12q14-15 (15 tumors). As in subgroups of pleomorphic adenomas of the salivary glands, leiomyomas of the uterus, and lipomas with 12q14-15 abnormalities the HMGI-C gene is frequently rearranged we tested PCH with either 12q14-15 abnormalities or normal karyotype by FISH and 3' RACE experiments for rearrangements of HMGI-C. Rearrangements were found in all cases with chromosomal 12q14-15 abnormalities and further six cases with an apparently normal karyotype. By the combination of cytogenetics with molecular techniques the percentage of cases with intragenic rearrangements of HMGI-C or rearrangements of its immediate surrounding was thus increased to 70% (21/30 cases). Considering all types of aberrations within this series 80% (24/30) of all PCH were aberrant. This is the first report on a combined molecular and cytogenetic analysis of a large series of pulmonary chondroid hamartomas indicating that rearrangements of HMGI-C, a member of the high mobility group protein gene family, are the leading molecular events in the genesis of PCH.
Kazmierczak
B
B
Center for Human Genetics and Genetic Counselling, University of Bremen, Germany.
Rosigkeit
J
J
Wanschura
S
S
Meyer-Bolte
K
K
Van de Ven
W J
WJ
Kayser
K
K
Krieghoff
B
B
Kastendiek
H
H
Bartnitzke
S
S
Bullerdiek
J
J
D000328:Adult; D000368:Aged; D001483:Base Sequence; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D025063:Chromosome Disorders; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12; D017931:DNA Primers; D005091:Exons; D005260:Female; D015321:Gene Rearrangement; D025743:HMGA2 Protein; D006222:Hamartoma / Q000235:genetics* / Q000473:pathology; D006609:High Mobility Group Proteins / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008168:Lung / Q000002:abnormalities* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics; D016133:Polymerase Chain Reaction
D017931:DNA Primers; D025743:HMGA2 Protein; D006609:High Mobility Group Proteins; D010750:Phosphoproteins