Germline Mutation in KIF1Bβ Gene Associated with Loss of Heterozygosity: Usefulness of Next-Generation Sequencing in the Genetic Screening of Patients with Pheochromocytoma

Giuseppina De Filpo; Elisa Contini; Viola Serio; Andrea Valeri; Massimiliano Chetta; Daniele Guasti; Daniele Bani; Massimo Mannelli; Elena Rapizzi; Michaela Luconi; Mario Maggi; Tonino Ercolino; Letizia Canu

doi:10.1155/2020/3671396

Germline Mutation in KIF1Bβ Gene Associated with Loss of Heterozygosity: Usefulness of Next-Generation Sequencing in the Genetic Screening of Patients with Pheochromocytoma

Int J Endocrinol. 2020 May 30:2020:3671396. doi: 10.1155/2020/3671396. eCollection 2020.

Authors

Giuseppina De Filpo^{1

2}, Elisa Contini³, Viola Serio¹, Andrea Valeri⁴, Massimiliano Chetta⁵, Daniele Guasti⁶, Daniele Bani⁶, Massimo Mannelli^{1

2}, Elena Rapizzi⁶, Michaela Luconi^{1

2}, Mario Maggi^{1

2}, Tonino Ercolino², Letizia Canu^{1

2}

Affiliations

¹ Dept. of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
² Endocrinology Unit, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.
³ Center of Research and Innovation of Myeloproliferative Neoplasms, AOU Careggi, University of Florence, Florence, Italy.
⁴ General and Surgical Unit, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.
⁵ A.O.R.N. Cardarelli, Medical Genetics, Pad. Y, Naples, Italy.
⁶ Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.

Abstract

The genetic approach of pheochromocytomas and paragangliomas has changed in the last two decades. Nowadays, we know that more than 40% of patients have a germline mutation in one of the susceptibility genes identified to date. Our aim is to underline how genetic diagnosis by next-generation sequencing (NGS) can improve the management of patients affected by pheochromocytomas and paragangliomas in our routine diagnostic screening. We reported a case presentation and next-generation sequencing analysis supported by in silico studies and evaluation of mitochondrial status in KIF1Bβ tissue. A 46-year-old male affected by a left secreting pheochromocytoma underwent surgery in 2017. After surgery, the normetanephrine levels decreased very slowly and a suspected abdominal lymph node was detected. We found a novel germline KIF1Bβ gene mutation, c.4052C > T, p. Pro1351Leu associated with tumor loss of heterozygosity, and resulted likely-pathogenetic by in silico studies. This mutation was also associated with an increased number of mitochondria through the electron microscopy compared with wild-type tissues as suggestive for mitochondria neoformation compensatory to the mitochondrial autophagic figures observed. Our results underline the usefulness of next-generation sequencing in the presence of multiple tumor predisposition genes and how, at the same time, its use may result challenging for the clinicians. To date, performing the genetic analysis according to the latest Consensus Statement is mandatory in patients affected by PHEO/PGL.