Somatotroph Tumors and the Epigenetic Status of the Locus

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2021 Jul 24

PMID 34299200

Citations 5

Authors

Pauline Romanet

Justine Galluso

Peter Kamenicky

Mirella Hage

Marily Theodoropoulou

Catherine Roche

Thomas Graillon

Heather C Etchevers

Daniel De Murat

Gregory Mougel

Dominique Figarella-Branger

Henry Dufour

Thomas Cuny

Guillaume Assie

Anne Barlier

Affiliations

Soon will be listed here.

Abstract

Forty percent of somatotroph tumors harbor recurrent activating mutations, historically called the oncogene. In -negative somatotroph tumors, expression itself is highly variable; those with overexpression most resemble phenotypically those carrying the oncogene. is monoallelically expressed in the normal pituitary due to methylation-based imprinting. We hypothesize that changes in imprinting of -negative tumors affect expression levels and tumorigenesis. We characterized the locus in two independent somatotroph tumor cohorts: one of 23 tumors previously published (PMID: 31883967) and classified by pan-genomic analysis, and a second with 82 tumors. Multi-omics analysis of the first cohort identified a significant difference between -negative and -positive tumors in the methylation index at the known differentially methylated region (DMR) of the A/B transcript promoter, which was confirmed in the larger series of 82 tumors. allelic expression was analyzed using a polymorphic Fok1 cleavage site in 32 heterozygous -negative tumors. expression was significantly reduced in the 14 tumors with relaxed imprinting and biallelic expression, compared to 18 tumors with monoallelic expression. Tumors with relaxed imprinting showed significantly lower and expression levels. Altered A/B DMR methylation was found exclusively in -negative somatotroph tumors. 43% of -negative tumors showed imprinting relaxation, which correlated with lower , and expression, indicating lower sensitivity to somatostatin analogues and potentially aggressive behavior.

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