Dataset Information

Comparative proteomics of non-nodular and nodular skin tissues from a Hyaline Fibromatosis Syndrome patient.

ABSTRACT: Hyaline Fibromatosis Syndrome (HFS) is a rare genetic disorder caused by loss-of-function mutations in the gene CMG2. Patients develop subcutaneous nodules and painful joint contracture. CMG2 is a transmembrane protein of poorly understood physiological function. To understand better the pathogenesis of HFS and the role of CMG2 in this disease, we compared by mass-spectrometry the composition of nodular and matching non-nodular tissues. Two tissue pairs were analyzed, both obtained after surgical resection of nodules from a HFS patient. Our shotgun proteomics analysis showed that nodules were enriched in serum protein, which correlated with previous descriptions of blood vessel leakage in these tissues. Importantly, we also observed a clear accumulation of collagen VI in nodules. Collagen VI accumulation was caused by CMG2 loss-of-function and is the main cause of the nodule formation.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Skin

DISEASE(S): Autosomal Recessive Disease

SUBMITTER: Jérôme Bürgi

LAB HEAD: Gisou van der Goot

PROVIDER: PXD006268 | Pride | 2017-07-07

REPOSITORIES: Pride

ACCESS DATA

Publications

CMG2/ANTXR2 regulates extracellular collagen VI which accumulates in hyaline fibromatosis syndrome.

Bürgi Jérôme J Kunz Béatrice B Abrami Laurence L Deuquet Julie J Piersigilli Alessandra A Scholl-Bürgi Sabine S Lausch Ekkehart E Unger Sheila S Superti-Furga Andrea A Bonaldo Paolo P van der Goot F Gisou FG

Nature communications 20170612

Loss-of-function mutations in capillary morphogenesis gene 2 (CMG2/ANTXR2), a transmembrane surface protein, cause hyaline fibromatosis syndrome (HFS), a severe genetic disorder that is characterized by large subcutaneous nodules, gingival hypertrophy and severe painful joint contracture. Here we show that CMG2 is an important regulator of collagen VI homoeostasis. CMG2 loss of function promotes accumulation of collagen VI in patients, leading in particular to nodule formation. Similarly, collag ...[more]

PMID: 28604699

Similar Datasets

Project description:Hepatocarcinogenesis is a multi-stage process in which precursor lesions progress into early hepatocellular carcinomas (eHCC) by sequential accumulation of multiple genetic and epigenetic alterations. To decode the molecular events during early stages of liver carcinogenesis, we performed gene expression profiling on cirrhotic (regenerative) and dysplastic nodules (DN) as well as eHCC. Although considerable heterogeneity was observed at the regenerative and dysplastic stages, clear differences were detected between DN and eHCC which included 460 differentially expressed genes. Functional analysis of the significant gene set identified the MYC oncogene as a plausible driver gene for malignant conversion of the dysplastic nodules. In addition, gene set enrichment analysis (GSEA) revealed a remarkable enrichment of MYC up-regulated gene set in eHCC versus dysplasia. Presence of the MYC signature significantly correlated with increased expression of CSN5 as well as with the higher overall transcription rate of genes located in the 8q chromosome region. Furthermore, a classifier constructed from MYC target genes could robustly discriminate eHCC from high- and low-grade dysplastic nodules. In conclusion, our study identified unique expression patterns associated with the transition of high-grade dysplastic nodules to early HCC and demonstrated that activation of the MYC transcription signature is critical for the malignant conversion of pre-neoplastic liver lesions. Samples from forty-nine nodular liver lesions including 24 regenerative (cirrhotic) nodules (CN), 3 low-grade (LGDN), 12 high-grade dysplastic nodules (HGDN) and 10 early hepatocellular carcinomas (Early HCC) were used. The Human Operon V2 oligonucleotide library containing 22K features representing expressed sequences was printed to glass arrays in the Advanced Technology Center (National Cancer Institute, Gaithersburg, MD). The aRNA probes were fragmented and hybridized to the microarray slides following the standard procedures. All samples were hybridized against a common amplified reference RNA pooled from normal liver samples. Experimental duplicates were prepared following a reverse-flour design.

Dataset Information

Comparative proteomics of non-nodular and nodular skin tissues from a Hyaline Fibromatosis Syndrome patient.

Publications

CMG2/ANTXR2 regulates extracellular collagen VI which accumulates in hyaline fibromatosis syndrome.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure