By reviewing more than 1700 reported cases of hereditary PCC and PGL, a thorough summary of the genetics and clinical features of these tumors is given, both as part of the classical syndromes such as multiple endocrine neoplasia type 2 (MEN2), von Hippel-Lindau disease, neurofibromatosis type 1, and succinate dehydrogenase-related PCC-PGL and within syndromes associated with a smaller fraction of PCCs/PGLs, such as Carney triad, Carney-Stratakis syndrome, and MEN1.
This editorial summarizes some of these advances: the identification of the AIP, and the PDE11A and PDE8B genes by genome-wide association (GWA) studies as predisposing genes for pituitary and adrenal tumours, respectively, the discovery of p27 mutations in a new form of MEN similar to MEN type 1 (MEN 1) that is now known as MEN 4, the molecular investigations of Carney triad (CT), a disorder that associates paragangliomas (PGLs), gastrointestinal stromal tumour (GISTs), and pulmonary chondromas (PCH) with pheochromocytomas and adrenocortical adenomas and other lesions, and the molecular elucidation of the association of GISTs with paragangliomas (Carney-Stratakis syndrome) that is now known to be because of SDHB, SDHC, and SDHD mutations.
To understand the roles of the two tumor-suppressor genes and LOH on chromosome 11q in Chinese patients with sporadic PCC or PGL, we performed mutation detection of the SDHD and Men1 genes in tumors from 35 Chinese patients with PCC/PGL; we also did LOH analysis at chromosome 11q for 25 patients out of the 35.
MEN1 is characterized by parathyroid, pancreatic islet and anterior pituitary tumours, whilst MEN2 is characterized by medullary thyroid carcinoma (MTC) in association with phaeochromocytoma.
Although weak expression of MEN1 mRNA also was detected in pheochromocytoma on RT-PCR, menin expression was not detected in any case of pheochromocytoma by Western blot analysis, possibly due to the lower sensitivity of this assay compared with RT-PCR.
Extension of the screening program can now be anticipated for other inherited forms of MTC, such as familial MTC without pheochromocytoma or other endocrinological tumor syndromes such as MEN1 for which the locus has also recently been mapped.