Molecular cytogenetic characterization of a metastatic lung sarcomatoid carcinoma: 9p23 neocentromere and 9p23-p24 amplification including JAK2 and JMJD2C.
Sarcomatoid carcinoma of the lung (LSC) is a rare lung cancer characterized by an admixture of carcinoma and sarcoma components. Data concerning the genomic alterations of LSC are almost nonexistent. Here, we report on the first molecular cytogenetic characterization of a metastatic LSC. Cytogenetic and multicolor fluorescence in situ hybridization (M-FISH) analyses showed a near-triploid karyotype with numerous structural aberrations and four to six small supernumerary marker chromosomes containing chromosome 9 sequences. Comparative genomic hybridization on arrays (array CGH) detected an amplification of 9p23 approximately p24.3 and gains of 1q11 approximately q23.3, 3q26.2 approximately q29, and 17q23.2 approximately q24.1. The 9p amplification was also detected in the primary tumor and another metastasis of the same patient, indicating it was a significant element in the pathogenesis of this LSC case. Complementary FISH analysis showed that the small supernumerary chromosomes were isochromosomes for 9p23 approximately p24.3. These isochromosomes were lacking alpha-satellite sequences although they were still stable after 55 passages in culture. As demonstrated by immunostaining with anti-centromere antibodies, they contained a functional centromere. So-called analphoid "neocentromeres" are rare and have been mainly described in constitutional abnormal karyotypes. This case is the third description of the identification of neocentromeres in cancer, (i.e. well-differentiated liposarcoma and acute myeloid leukemia), and is the first one in a carcinoma. Our results suggest that the 9p23 neocentromere of this case of LSC might be similar to a 9p23 neocentromere previously identified in two constitutional cases. The frequency of neocentromere formation in solid tumors may indeed be underestimated and may have a significant implication in chromosomal instability in tumor cells.
Italiano
Antoine
A
Laboratory of Solid Tumors Genetics, Centre Hospitalier Universitaire de Nice and CNRS UMR 6543, Faculté de Medecine, 28 avenue de Valombrose, 06107 Nice, France.
Attias
Rita
R
Aurias
Alain
A
Pérot
Gaëlle
G
Burel-Vandenbos
Fanny
F
Otto
Josiane
J
Venissac
Nicolas
N
Pedeutour
Florence
F
D000782:Aneuploidy; D002277:Carcinoma / Q000556:secondary*; D002503:Centromere; D002869:Chromosome Aberrations; D002899:Chromosomes, Human, Pair 9 / Q000648:ultrastructure; D005784:Gene Amplification; D006801:Humans; D017403:In Situ Hybridization; D053614:Janus Kinase 2; D056484:Jumonji Domain-Containing Histone Demethylases; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D009693:Nucleic Acid Hybridization; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012509:Sarcoma / Q000556:secondary*; D014157:Transcription Factors / Q000235:genetics
C413655:KDM4C protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D056484:Jumonji Domain-Containing Histone Demethylases; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2