Intraosseous hibernoma: clinicopathologic and imaging analysis of 18 cases.

AIMS: Intraosseous hibernomas are rarely reported tumours with brown adipocytic differentiation of unknown aetiology, with only 38 cases documented in the literature. We sought to further characterise the clinicopathologic, imaging and molecular features of these tumours. METHODS AND RESULT: Eighteen cases were identified occurring in eight females and 10 males (median age = 65 years, range = 7-75). Imaging indication was cancer surveillance/staging in 11 patients and clinical concern for a metastasis was raised in 13 patients. The innominate bone (7), sacrum (5), mobile spine (4), humerus (1) and femur (1) were involved. Median tumour size was 1.5 cm (range = 0.8-3.8). Tumours were sclerotic (11), mixed sclerotic and lytic (4) or occult (1). Microscopically, tumours were composed of large polygonal cells with distinct cell membranes, finely vacuolated cytoplasm, central or paracentral small bland nuclei with prominent scalloping. Growth around trabecular bone was observed. Tumour cells were immunoreactive for S100 protein (15/15) and adipophilin (5/5), while negative for keratin AE1/AE3(/PCK26) (0/14) and brachyury (0/2). Chromosomal microarray analysis, performed on four cases, did not show clinically significant copy number variation across the genome or on 11q, the site of AIP and MEN1. CONCLUSION: Analysis of 18 cases of intraosseous hibernoma, to our knowledge, the largest series to date, revealed that these tumours are most often detected in the spine and pelvis of older adults. Tumours were generally small, sclerotic and frequently found incidentally and can raise concern for metastasis. Whether or not these tumours are related to soft tissue hibernomas is uncertain.

Trithorax, Hox, and TALE-class homeodomain proteins ensure cell survival through repression of the BH3-only gene egl-1.

Mutations that aberrantly activate trithorax-group proteins, Hox transcription factors and TALE-class Hox cofactors promote leukemogenesis, but their target genes critical for leukemogenesis remain largely unknown. Through genetic analyses in C. elegans, we find that the trithorax-group gene lin-59 and the TALE-class Hox cofactor unc-62 are required for survival of the VC motor neurons. With the goal of providing a model for how aberrantly active Hox complexes might promote leukemia, we elucidate the mechanism through which these new inhibitors of programmed cell death act: lin-59 maintains transcription of the Hox gene lin-39, while unc-62 promotes nuclear localization of the TALE-class Hox cofactor ceh-20. A LIN-39/CEH-20 complex binds the promoter of the pro-apoptotic BH3-only gene egl-1, repressing its transcription and ensuring survival of the VC neurons. In the absence of this regulatory mechanism, egl-1 is transcribed and the VC neurons die. Furthermore, ectopic expression of the Hox gene lin-39, as occurs for human Hox genes in leukemia, is sufficient to block death of some cells. This work identifies BH3-only pro-apoptotic genes as targets of Hox-mediated repression and suggests that aberrant activation of Hox networks may promote leukemia in part by inhibiting apoptosis.

MIG-32 and SPAT-3A are PRC1 homologs that control neuronal migration in Caenorhabditis elegans.

The Polycomb repression complex 2 (PRC2) methylates histone H3 lysine 27 at target genes to modify gene expression, and this mark is recognized by PRC1, which ubiquitylates histone H2A. In Caenorhabditis elegans, a complex of the MES-2, MES-3 and MES-6 proteins is functionally analogous to the PRC2 complex, but the functional analog of PRC1, and indeed whether C. elegans has such a complex, has been unclear. We describe here that MIG-32 and SPAT-3A are functional analogs of PRC1 in C. elegans, where they are required for neuronal migrations and during vulval development. mig-32 and spat-3 mutants are defective in H2A ubiquitylation, and have nervous system defects that partially overlap with those of mes mutants. However, unlike the mes mutants, mig-32 and spat-3 mutants are fertile, suggesting that PRC1 function is not absolutely required in the germline for essential functions of PRC2.