We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
Abbott Diagnostics- Hematology Division

AGILENT

  Silver Agilent provides laboratories worldwide with instruments, services, consumables, applications and expertise, enabling... read more Featured Products: More products

Download Mobile App




Events

ATTENTION: Due to the COVID-19 PANDEMIC, many events are being rescheduled for a later date, converted into virtual venues, or altogether cancelled. Please check with the event organizer or website prior to planning for any forthcoming event.
23 Sep 2021 - 25 Sep 2021

Benign Hypertension-Causing Tumors Linked to Somatic Co-Driver Mutations

By LabMedica International staff writers
Posted on 26 Aug 2021
Print article
Image: The Agilent TapeStation system is an established automated electrophoresis tool for DNA and RNA sample quality control (Photo courtesy of Agilent Technologies)
Image: The Agilent TapeStation system is an established automated electrophoresis tool for DNA and RNA sample quality control (Photo courtesy of Agilent Technologies)
Most aldosterone-producing adenomas (APAs) have gain-of-function somatic mutations of ion channels or transporters. However, their frequency in aldosterone-producing cell clusters of normal adrenal gland suggests a requirement for co-driver mutations in APAs.

Primary aldosteronism is a major cause of hypertension. This is potentially curable when due to an APA in one adrenal. Conversely, when primary aldosteronism (PA) is overlooked, it leads to resistant hypertension and high cardiovascular risk. The genes whose mutation increases aldosterone production may differ from those responsible for tumor formation.

An international team of Biomedical Scientists led by the Queen Mary University of London (London, UK) group performed whole-exome sequencing on matched tumor and germline samples from 41 individuals with APA, identifying hotspot somatic mutations in ion channel or transporter genes such as CACNA1D or KCNJ5 in dozens of the samples. Genomic DNA of samples was quality assessed by gel electrophoresis, Agilent 2200 Tapestation and Genomic DNA screentape (Agilent Technologies, Santa Clara, CA, USA), or as per GATC Biotech (Ebersberg, Germany), The team used the HiSeq 2000 Sequencer, the NextSeq 500 Sequencer and the HiSeq 2500 sequencer (Illumina, San Diego, CA, USA) on extracted genomic DNA samples.

The investigators reported the whole-exome sequencing identified somatic mutations of the four ion channel/transporter genes at known hotspots in 29 of the 41 APAs. Somatic mutations of CACNA1D were the most frequent (n = 11), followed by KCNJ5 (n = 9), ATP1A1 (n = 5) and ATP2B3 (n = 4). Three APAs had a known mutation of CTNNB1 and all three were noted to have a second mutation of the Q209 residue of GNA11, which encodes the G-protein G11. Among multiple transcripts upregulated more than tenfold in double-mutant APAs was LHCGR, the receptor for luteinizing or pregnancy hormone (human chorionic gonadotropin). Transfections of adrenocortical cells demonstrated additive effects of GNA11 and CTNNB1 mutations on aldosterone secretion and expression of genes upregulated in double-mutant APAs. In adrenal cortex, GNA11/Q mutations appear clinically silent without a co-driver mutation of CTNNB1.

The authors concluded that onset of hypertension in the first trimester, the period of peak human chorionic gonadotropin (HCG) secretion, should prompt consideration of PA. Most pregnancy-associated hypertension arises in later trimesters. Patients are diagnosed relatively quickly because of the explosive onset of PA, when the 'dormant' LHCGR sees its stimulatory hormone. The study was published on August 12, 2021 in the journal Nature Genetics.

Related Links:
Queen Mary University of London
Agilent Technologies
GATC Biotech
Illumina


Gold Supplier
Microplate Washer
MW-12A
New
Clinical Chemistry Analyzer
Mispa CXL Pro
New
Methicillin-Resistant Staphylococcus Aureus RT PCR Test
VIASURE Methicillin-Resistant Staphylococcus Aureus Real Time PCR Detection Kit
New
Silver Supplier
SARS-CoV-2 Antigen Test
NG-Test SARS-NG-Test SARS-CoV-2 Ag Cassette

Print article

Channels

Pathology

view channel
Image: The CellSearch Circulating Tumor Cell Kit is intended for the enumeration of circulating tumor cells of epithelial origin (CD45-, EpCAM+, and cytokeratins 8, 18+, and/or 19+ and PD-L1) in whole blood (Photo courtesy of CellSearch/Menarini Silicon Biosystems)

PD-L1 Expression in Circulating Tumor Cells Investigated for NSCLC

In non-small cell lung cancer (NSCLC), analysis of programmed cell death ligand 1 (PD-L1) expression in circulating tumor cells (CTCs) is a potential alternative to overcome the problems linked to the... Read more

Industry

view channel
Illustration

Global Digital Polymerase Chain Reaction (dPCR) Market Projected to Reach Close to USD 1.15 Billion by 2028

The global digital polymerase chain reaction (dPCR) market is projected to grow at a CAGR of more than 9% from over USD 0.50 billion in 2020 to nearly USD 1.15 billion by 2028, driven primarily by rising... Read more
Copyright © 2000-2021 Globetech Media. All rights reserved.