PhD Scientific Days 2017

Oral Presentations: Oncology

Phenotype modifiers in patients with germline SDHB mutations

Előadó neve

Dr. Sarkadi, Balázs

Előadó munkahelye

Semmelweis University

Előadó telefonszáma

+36304525803

Előadó e-mail címe

sharkadi@gmail.com

Az előadás címe

Phenotype modifiers in patients with germline SDHB mutations

Szerző(k) neve és munkahelye

Balázs Sarkadi1,2, Istvan Liko1,3, Otto Darvasi1, Károly Rácz2,3,4 , Attila Patócs1,3, 5
1 HAS-SE “Lendulet” Hereditary Endocrine Tumors Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary
2 2nd Department of Medicine, Semmelweis University, Budapest, Hungary
3 Bionics Innovation Center, Budapest, Hungary
4 HAS-SE Molecular Medicine Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary
5 Department of Laboratory Medicine, Semmelweis University, Budapest, Hungary

Szekció

Oral Presentations: Oncology

Data of the presenter

Doctoral School: Clinical Medicine
Program: Hormonal Regulations
Supervisor: Attila Patócs
email: sarkadi.balazs2@med.semmelweis-univ.hu

Text of the abstract

INTRODUCTION: Genetic background of pheochromocytoma/paraganglioma (Pheo/PGL) consists of 15 genes of which germline mutations can be identified in approximately 40% of patients. The clinical phenotype is remarkably heterogeneous, several genotype-phenotype associations have been described. The most important is the aggressive malignant phenotype associating with SDHB mutations. The mechanism behind this phenomenon is not understood completely yet, but genetic variations in certain genes could alter the phenotype observed in patients with inherited cancer syndromes.
AIMS: To assess the sensitivity and specificity of whole exome sequencing (WES) in Pheo/PGL associated genes and the identification of phenotype altering variants in patients with germline SDHB mutations.
METHODS: WES was performed on 20 DNA samples obtained from patients on whom previously mutation analysis with Sanger sequencing was carried out for all exons of SDHB, SDHC, SDHD, VHL, RET, TMEM127 and MAX genes. Bioinformatic analysis and validation of WES were carried out. The newly identified likely pathogenic variants were validated with Sanger sequencing.
RESULTS: All previously detected pathogenic variants were identified with WES based on bioinformatic settings and filtering. 13 patient carried inherited mutations predisposing to Pheo/PGL (10 SDHB, 2 SDHD and 1 SDHC mutation). The coverage of targeted genes varied markedly between library preparation kits. Additional, potentially pathogenic variants in RET, EGLN1 and KIF1ß genes were identified in SDHB mutation carriers.
CONCLUSION: Whole exome sequencing is a cost-effective and efficient method for detection of germline mutations in Pheo/PGL associated genes. Additional variants which could participate in the development of the aggressive phenotype and may function as genetic modifiers can also be identified.

Kind

Szabad

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

1167

Authors (legacy)

Balázs Sarkadi1,2, Istvan Liko1,3, Otto Darvasi1, Károly Rácz2,3,4 , Attila Patócs1,3, 5
1 HAS-SE “Lendulet” Hereditary Endocrine Tumors Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary
2 2nd Department of Medicine, Semmelweis University, Budapest, Hungary
3 Bionics Innovation Center, Budapest, Hungary
4 HAS-SE Molecular Medicine Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary
5 Department of Laboratory Medicine, Semmelweis University, Budapest, Hungary