Mutated Gene Biomarker Identified for Rare Adrenal Tumors

A mutation in a gene has been found that may serve as a biomarker for the rare adrenal tumors pheochromocytomas and paragangliomas that become malignant.

Pheochromocytomas and paragangliomas (PCC/PGL) are tumors of the autonomic nervous system arising from the adrenal medulla and extra-adrenal ganglia, respectively. PCC/PGL are more commonly associated with inherited susceptibility gene mutations than any other solid tumor.


Scientists at the Perelman School of Medicine (Philadelphia, PA, USA) used a set of 21 PCC/PGL that were selected to represent clinically benign and clinically aggressive tumors. Fresh-frozen PCC/PGL were sectioned and stained with hematoxylin and eosin to ensure sections of over 70% tumors are used for DNA extraction. Germline DNA from blood or saliva was extracted using standard protocols in the laboratory.

All DNA was quantitated with a Qubit fluorometer (Life Technologies; Carlsbad, CA, USA). To ensure high-quality genomic DNA, the A260/280 ratio was measured on a Nanodrop (Wilmington, DE, USA) and DNA was run on a 1% agarose gel. Whole-exome sequencing was performed on fresh-frozen tumor and matched germline DNA and DNA quality and fragment size were measured with an Agilent 2100 Bioanalyzer (Santa Clara, CA, USA) and concentration measured with a Qubit fluorometer.

The team reported that somatic alpha thalassemia/mental retardation syndrome X-linked (ATRX) mutations were identified in two of seven succinate dehydrogenase complex, subunit B, iron sulfur (SDHB)-associated tumors. To determine the frequency of somatic ATRX mutations in PCC/PGL, the team sequenced the ATRX coding region in a separate set of 103 tumors samples. They found that 13% of tumors had ATRX mutations.

The authors concluded that although the sample set of PCC/PGL with ATRX variants is too small to identify statistically significant associations, many had clinically aggressive features, inherited succinate dehydrogenase (SDHx) mutations and alternative lengthening of telomeres (ALT), suggesting an interaction between the somatic and inherited genomes in solid cancers, which needs to be investigated further. The study was published on January 21, 2015, in the journal Nature Communications.

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