title: MAX mutations status in Swedish patients with pheochromocytoma and paraganglioma tumours.
abstract: Pheochromocytoma (PCC) and Paraganglioma are rare tumours originating from neuroendocrine cells. Up to 60% of cases have either germline or somatic mutation in one of eleven described susceptibility loci, SDHA, SDHB, SDHC, SDHD, SDHAF2, VHL, EPAS1, RET, NF1, TMEM127 and MYC associated factor-X (MAX). Recently, germline mutations in MAX were found to confer susceptibility to PCC and paraganglioma (PGL). A subsequent multicentre study found about 1% of PCCs and PGLs to have germline or somatic mutations in MAX. However, there has been no study investigating the frequency of MAX mutations in a Scandinavian cohort. We analysed tumour specimens from 63 patients with PCC and PGL treated at Uppsala University hospital, Sweden, for re-sequencing of MAX using automated Sanger sequencing. Our results show that 0% (0/63) of tumours had mutations in MAX. Allele frequencies of known single nucleotide polymorphisms rs4902359, rs45440292, rs1957948 and rs1957949 corresponded to those available in the Single Nucleotide Polymorphism Database. We conclude that MAX mutations remain unusual events and targeted genetic screening should be considered after more common genetic events have been excluded.
authors.affiliation: Department of Surgical, Uppsala University, Akademiska sjukhuset, ing 70, 3tr, FOA2, 75185, Uppsala, Sweden, joakim.crona@surgsci.uu.se.
authors.forename: Joakim
authors.initials: J
authors.lastname: Crona
authors.forename: Rajani
authors.initials: R
authors.lastname: Maharjan
authors.forename: Alberto
authors.initials: A
authors.lastname: Delgado Verdugo
authors.forename: Peter
authors.initials: P
authors.lastname: Stålberg
authors.forename: Dan
authors.initials: D
authors.lastname: Granberg
authors.forename: Per
authors.initials: P
authors.lastname: Hellman
authors.forename: Peyman
authors.initials: P
authors.lastname: Björklund
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010235:Paraganglioma / Q000235:genetics*; D010673:Pheochromocytoma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D013548:Sweden
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C499330:MAX protein, human