Article

Clinicopathological Characterization and Genomic Aberrations in Subcutaneous Panniculitis-Like T-Cell Lymphoma

Department of Dermatology and Allergology, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.
Journal of Investigative Dermatology (Impact Factor: 6.37). 04/2008; 128(9):2304-9. DOI: 10.1038/jid.2008.6
Source: PubMed

ABSTRACT Subcutaneous panniculitis-like T-cell lymphomas (SPTLs) represent a rare, difficult-to-diagnose, and poorly characterized subtype of cutaneous T-cell lymphomas (CTCLs) affecting younger people more than the other CTCL forms. We performed a thorough clinical, immunohistological, and molecular analysis of nine Finnish SPTL patients. Specifically, we performed single-cell comparative genomic hybridization (CGH) from laser microdissected, morphologically malignant SPTL cells, as well as loss of heterozygosity (LOH) and fluorescence in situ hybridization (FISH) analysis for the NAV3 (neuron navigator 3) gene. CGH revealed large numbers of DNA copy number changes, the most common of which were losses of chromosomes 1pter, 2pter, 10qter, 11qter, 12qter, 16, 19, 20, and 22 and gains of chromosomes 2q and 4q. Some of the DNA copy number aberrations in SPTL, such as loss of 10q, 17p, and chromosome 19, overlap with those characteristic of common forms of CTCL (mycosis fungoides (MF) and Sezary syndrome (SS)), whereas 5q and 13q gains characterize SPTL. Allelic NAV3 aberrations (LOH or deletion by FISH), previously found in MF and SS, were identified in 44% of the SPTL samples. This study demonstrates that SPTL is also moleculocytogenetically a uniform entity of CTCL and supports the current World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) classification defining SPTL as a subgroup of its own.

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    • "The NAV1 and NAV2 proteins have been reported to localize in the centrosomes and to be involved in the mitotic process (van Haren et al., 2009), nervous system development and regeneration , neural tumorigenesis (Coy et al., 2002), and cell migration events even beyond the nervous system (Klein et al., 2011). In tumors, NAV3 transcript expression is downregulated in 40% of primary neuroblastomas (Coy et al., 2002), and NAV3 is deleted or translocated in several subtypes of cutaneous T-cell lymphomas (Karenko et al., 2005; Vermeer et al., 2008; Hahtola et al., 2008a). We have identified NAV3 gene copy number changes (deletions/amplifications) also in cancers of epithelial origin, especially in colorectal cancers (Hahtola et al., 2008b; Carlsson et al., 2012). "
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    • "We have previously shown that chromosome 12q21 aberrations, specifically allelic loss of the neuron navigator 3 (NAV3) gene, are associated with several subtypes of cutaneous T-cell lymphoma (CTCL; Karenko et al, 2005; Hahtola et al, 2008a), CTCL-associated lung cancers (Hahtola et al, 2008b), and ca. 25% of cutaneous basal and squamous cell cancers (Maliniemi et al, 2011). "
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    • "Although some of the subsequent studies by other groups failed to confirm this finding (Carbone et al., 2008; Marty et al., 2008), the discrepancy might be explained by the different case series analyzed or by the different detection methods used in these studies (Karenko et al., 2005; Carbone et al., 2008; Marty et al., 2008; Vermeer et al., 2008). Allelic NAV3 deletion has also been shown to have a role in the oncogenesis of subcutaneous panniculitis-like T-cell lymphoma (Hahtola et al., 2008a) and other cancers (Hahtola et al., 2008b; Bleeker et al., 2009; Soon et al., 2009). Importantly, NAV3 gene deletion may be a relatively early event in the development of MF, because it was found in 50% of the early MF cases (Karenko et al., 2005). "
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