Disease relevance of Lipoma

• Multiple endocrine neoplasia 1 gene alterations in MEN1-associated and sporadic lipomas [1].
• Unregulated proliferation of mesenchymal cells in leiomyomas, lipomas, hamartomas,and other diseases has been linked to the high mobility group (HMGA) family of DNA architectural proteins [2].
• Pulsed-field analysis of myxoid liposarcoma and lipoma DNA has allowed us to construct a 600-kilobase physical map surrounding the GLI locus, which shows that breakpoints in both types of tumor are outside this region [3].
• HMGI-C expression was detected in 7 of 11 ordinary lipomas (63.6%) with alterations at 12q14-15 and in one case with an abnormal karyotype that included double minute chromosomes [4].
• Caveolin-1 was found to be expressed in fibromatoses, leiomyomas, hemangiomas, and lipomas at high levels comparable to normal mesenchymal tissues [5].

High impact information on Lipoma

• Disruption of the architectural factor HMGI-C: DNA-binding AT hook motifs fused in lipomas to distinct transcriptional regulatory domains [6].
• Metastatic hibernomas in transgenic mice expressing an alpha-amylase-SV40 T antigen hybrid gene [7].
• No such hibernoma occurred in P2-TAg transgenic mice [8].
• Similar truncations of murine Hmga2 in transgenic mice result in somatic overgrowth and, in particular, increased abundance of fat and lipomas, features strikingly similar to those observed in the child [9].
• To determine whether other syndromes characterized by overgrowth and lipomas are part of the PTEN syndrome spectrum, we ascertained six individuals with overgrowth and lipomas but who did not meet the diagnostic criteria for CS or BRR [10].

Chemical compound and disease context of Lipoma

• Melatonin inhibition of cancer growth in vivo involves suppression of tumor fatty acid metabolism via melatonin receptor-mediated signal transduction events [11].
• Development of multiple lipomas during treatment with rosiglitazone in a patient with HIV-associated lipoatrophy [12].
• The data suggest that fat mobilization from the lipoma is impaired, and that this is due to resistance to the effect of cyclic AMP on hormone sensitive lipase [13].
• This is the first case of intramedullary lipoma of the spinal cord that may be related to steroid use [14].
• In the phospholipid fatty acids of mammary cancers there was a marked increase in the relative amounts of unsaturated fatty acids, especially arachidonic acid, while saturated fatty acids were decreased, as compared with a healthy reference breast tissue or lipomas [15].

Biological context of Lipoma

• Chromosome 12 breakpoints are cytogenetically different in benign and malignant lipogenic tumors: localization of breakpoints in lipoma to 12q15 and in myxoid liposarcoma to 12q13.3 [16].
• We have therefore undertaken studies to search for such mutations in six MEN type 1 tumors (four parathyroid tumors, one insulinoma, and one lipoma) that did not have LOH at 11q13 as assessed using the flanking markers D11S480, D11S1883 and PYGM centromerically and D11S449 and D11S913 telomerically [17].
• The correlation between ring chromosomes and MDM2 gene amplification indicates that the marker rings of MFH and of atypical lipoma often harbor genetic material derived from chromosome 12 [18].
• Rearrangements of HMGA1 and HMGA2 genes, consequent to chromosomal translocation, have been frequently detected in human benign tumours of mesenchymal origin including lipomas [19].
• A major cytogenetic subgroup among human lipomas is characterized by translocations involving the HMGIC gene at 12q15 [20].

Anatomical context of Lipoma

• Translocations of 12q13-15 in lipomas (fat cell tumors) disrupt HMGI-C and fuse its DNA-binding domains to novel transcriptional regulatory domains [21].
• An analysis of four cases of lipomas of the corpus callosum with epilepsy, and a review of the literature, have led to the following conclusions: (1) Epilepsy as an almost constant feature is often severe, nearly always partial, and begins before the age of 15 [22].
• Benign mesenchymal neoplasms associated with rearrangements of the DNA architectural factor gene HMGIC on chromosome 12 include lipomas, uterine leiomyomata, pulmonary chondroid hamartomas, endometrial polyps, salivary gland pleomorphic adenomas, and breast fibroadenomas [23].
• Calretinin immunoreactivity was detected, at least focally, in all 10 samples of normal adipose tissue and in 22 of 23 lipomas or lipoma variants [24].
• Monovacuolar cells in normal white fat tissue and in lipomas generally exhibited a distinctive pericellular basement membrane composed of collagen IV and laminin, whereas heparan sulfate proteoglycan and fibronectin were almost completely missing [25].

Gene context of Lipoma

• Additionally, the presence of lipomas was correlated with the presence of PTEN mutation in BRR patients ( P = 0.028) [26].
• All lipomas were mdm2-negative. cdk4 overexpression was present in 100% of ALTs [27].
• Rearrangements of the HMGA2 gene have been frequently detected in human benign tumors of mesenchymal origin including lipomas [28].
• These results suggest a critical role played by HMGA1 rearrangements in the generation of human lipomas [19].
• LPP, the preferred fusion partner gene of HMGIC in lipomas, is a novel member of the LIM protein gene family [29].

Analytical, diagnostic and therapeutic context of Lipoma

• As for diagnostic significance, the absence of mdm2 and p53 reactivity in lipomas seems to represent a useful marker for differential diagnosis from lipoma-like WD liposarcomas [30].
• To investigate further a possible role of the two genes in sarcomas, 24 large and deep-seated lipomas and 74 liposarcomas of various subtypes were analysed for mdm2 and p53 overexpression by immunocytochemistry [30].
• RT-PCR analysis revealed that HMGA2-LPP transcripts in lipomas with the fusion were 591-fold of full-length HMGA2 transcripts in lipomas without the fusion [31].
• Hibernomas show intense accumulation of FDG positron emission tomography [32].
• Eleven benign lipogenic tumors comprising ten ordinary lipomas and one fibroblastic lipoma were studied by light and electron microscopy [33].

References