Scholarlink

<p>Bilateral macronodular adrenocortical disease (BMAD) is currently described as composed of 4 microscopic subtypes (subtype 1 to 4) and 3 molecular groups (<i>ARMC5</i>-altered, <i>KDM1A</i>-altered, and unknown). Little is known about protein heterogeneity and its links with BMAD characteristics. The aim of this work is to study the protein signatures of BMADs and their correlations with microscopy and genetics. Liquid chromatography and tandem mass spectrometry (LC-MS/MS) was performed on 24 BMADs: 7 <i>ARMC5</i>, 4 <i>KDM1A</i>, 13 non-<i>KDM1A</i>, non-<i>ARMC5</i> BMADs and 2 normal adrenal glands and 10 adrenal adenomas as control. Unsupervised clustering divided BMAD samples into 3 proteomic groups. The first group is composed of <i>ARMC5</i>-altered BMADs (subtype 1) and is characterized by an accumulation of RNA polymerase II (Pol II) subunits. The second, composed of <i>KDM1A</i>-altered (subtype 2) patients and subtype 4 BMADs (oncocytic), is characterized by an accumulation of cholesterol biosynthesis enzymes (such as FDFT1). The last group has no specific signature detected and is composed of subtypes 1 and 3 BMAD without <i>ARMC5</i> alteration. Immunohistochemical analyses with anti Pol II subunits and cholesterol biosynthesis enzymes correlate with the three proteomic groups. Proteins specifically accumulated in <i>ARMC5</i>-altered BMADS such as POLR2A could be used as biomarkers to detect <i>ARMC5</i> alterations. Data are available via ProteomeXchange with identifier PXD070500. Our study explores BMAD proteome using LC-MS/MS. The 3 proteomic groups mostly overlap the 4 microscopic and 3 molecular groups of BMAD. Accumulation of Pol II subunits consistent with the described role of <i>ARMC5</i> could play a role in the pathogenesis of these BMADs. <i>KDM1A</i>-altered (subtype 2) and subtype 4 BMADs showed an accumulation of proteins involved in lipid metabolism that could contribute to hypercortisolism. These results reveal specific protein patterns pointing to various cellular processes opening new perspectives to understand BMAD pathophysiology and provide new tools for the pathologists.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

The Proteome of Bilateral Macronodular Adrenocortical Disease (BMAD) Shows Different Profiles Correlating with the Genetic Causes and Reveals Specific Dysregulation of RNA Polymerase II and Cholesterol Biosynthesis Enzymes

  • 期刊论文

  • 发表日期：

    2026年1月12日

查看全文
  • Florian Violon,
  • Anne Jouinot,
  • Bruno Ragazzon,
  • Patricia Vaduva,
  • Lucas Bouys,
  • Louis Thomeret,
  • Johanna Bruce,
  • Marjorie Leduc,
  • Martin Gaillard,
  • Guillaume Assié,
  • Fidéline Bonnet-Serrano,
  • Annabel Berthon,
  • Mathilde Sibony,
  • Jérôme Bertherat

摘要

Bilateral macronodular adrenocortical disease (BMAD) is currently described as composed of 4 microscopic subtypes (subtype 1 to 4) and 3 molecular groups (ARMC5-altered, KDM1A-altered, and unknown). Little is known about protein heterogeneity and its links with BMAD characteristics. The aim of this work is to study the protein signatures of BMADs and their correlations with microscopy and genetics. Liquid chromatography and tandem mass spectrometry (LC-MS/MS) was performed on 24 BMADs: 7 ARMC5, 4 KDM1A, 13 non-KDM1A, non-ARMC5 BMADs and 2 normal adrenal glands and 10 adrenal adenomas as control. Unsupervised clustering divided BMAD samples into 3 proteomic groups. The first group is composed of ARMC5-altered BMADs (subtype 1) and is characterized by an accumulation of RNA polymerase II (Pol II) subunits. The second, composed of KDM1A-altered (subtype 2) patients and subtype 4 BMADs (oncocytic), is characterized by an accumulation of cholesterol biosynthesis enzymes (such as FDFT1). The last group has no specific signature detected and is composed of subtypes 1 and 3 BMAD without ARMC5 alteration. Immunohistochemical analyses with anti Pol II subunits and cholesterol biosynthesis enzymes correlate with the three proteomic groups. Proteins specifically accumulated in ARMC5-altered BMADS such as POLR2A could be used as biomarkers to detect ARMC5 alterations. Data are available via ProteomeXchange with identifier PXD070500. Our study explores BMAD proteome using LC-MS/MS. The 3 proteomic groups mostly overlap the 4 microscopic and 3 molecular groups of BMAD. Accumulation of Pol II subunits consistent with the described role of ARMC5 could play a role in the pathogenesis of these BMADs. KDM1A-altered (subtype 2) and subtype 4 BMADs showed an accumulation of proteins involved in lipid metabolism that could contribute to hypercortisolism. These results reveal specific protein patterns pointing to various cellular processes opening new perspectives to understand BMAD pathophysiology and provide new tools for the pathologists.