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Transcription profiling of yeast with a fumarase point mutation or knock-out to model hereditary leiomyomatosis and renal cell cancer

ABSTRACT: Effect of fumarase point mutation or knock-out on transcriptional profile in yeast to model hereditary leiomyomatosis and renal cell cancer (HLRCC).

ORGANISM(S): Saccharomyces cerevisiae

SUBMITTER: Jarno Tuimala

PROVIDER: E-MEXP-922 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Modeling tumor predisposing FH mutations in yeast: effects on fumarase activity, growth phenotype and gene expression profile.

Kokko Antti A Ylisaukko-Oja Sanna S K SS Kiuru Maija M Takatalo Maarit S MS Salmikangas Paula P Tuimala Jarno J Arango Diego D Karhu Auli A Aaltonen Lauri A LA Jäntti Jussi J

International journal of cancer 20060301 6

Heterozygous mutations in the fumarase (FH) gene cause the tumor predisposition syndrome hereditary leiomyomatosis and renal cell cancer (MIM 605839). While most families segregate a benign phenotype of multiple leiomyomas, others display a phenotype with early-onset renal cancer and leiomyosarcoma. Modifier genes may play a role in this, but an alternative explanation is simple genotype-phenotype association. FH mutations predisposing to cancer appear to be truncating or in fully conserved amin ...[more]

PMID: 16206287

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Proteogenomic Landscape of Uterine Leiomyomas from Hereditary Leiomyomatosis and Renal Cell Cancer Patients

Project description:Pathogenic mutations in fumarate hydratase (FH) drive hereditary leiomyomatosis and renal cell cancer (HLRCC) and increase the risk of developing uterine leiomyomas (ULMs). An integrated proteogenomic analysis of ULMs from HLRCC (n=16; FH-mutation confirmed) and non-syndromic (NS) patients (n=12) identified a significantly higher protein:transcript correlation in HLRCC (R=0.35) vs. NS ULMs (R=0.242, MWU p=0.0015). Co-altered proteins and transcripts (228) included antioxidant response element (ARE) target genes, such as thioredoxin reductase 1 (TXNRD1), and correlated with activation of NRF2-mediated oxidative stress response signaling in HLRCC ULMs. We confirm 185 transcripts previously described as altered between HLRCC and NS ULMs, 51 co-altered at the protein level and several elevated in HLRCC ULMs are involved in regulating cellular metabolism and glycolysis signaling. Furthermore, 367 S-(2-succino)cysteine peptides were identified in HLRCC ULMs, of which sixty were significantly elevated in HLRCC vs. NS ULMs (LogFC=1.86, MWU p<0.0001). These results confirm and define novel proteogenomic alterations in uterine leiomyoma tissues collected from HLRCC patients and underscore conserved molecular alterations correlating with inactivation of the FH tumor suppressor gene.

2021-12-15 | PXD024830 | Pride

DPYS as a potential diagnostic biomarker in hereditary and sporadic PRCC2

Project description:Papillary renal cell carcinoma type 2 (PRCC2) is known to be very aggressive type of tumor without effictive therapy. Hereditary form of PRCC2 is caused by Fumarate Hydratase (FH) gene mutation that accompanied Hereditary Leiomyomatosis and Renal Cell Carcinoma (HLRCC) disorder. In sporadic form of PRCC2 the mutation of FH gene has not been reported. Both forms of tumors have the similar histopathological characteristics with poor survival prognosis. In this study, we profiled the gene expression of renal tumors and normal tissue from PRCC2 (hereditary and sporadic) patients in order to better understand commonalities and differences in the transcriptional landscape of PRCC2.

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An antioxidant response phenotype is shared between hereditary and sporadic type 2 papillary renal cell carcinoma

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Gene expression profile of HLRCC associated renal cell cancer

Project description:Gene expression profiles of normal kidney (3 technical replicates) and a renal tumor (3 technical replicates) from a hereditary leiomyomatosis and renal cell cancer (HLRCC) patient carrying a germline mutation in the fumarate hydratase (FH) gene.

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Expression data of cystic renal epithelial tissue from mice deficient for fumarate hydratase.

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Expression data from mouse kidney epithelial cells

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Expression data from mouse kidney epithelial cells

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