Uncommon variants detected via hereditary cancer panel and suggestions for genetic counseling

Zeynep Özdemir; Ezgi Çevik; Ömür Berna Çakmak Öksüzoğlu; Mutlu Doğan; Öztürk Ateş; Ece Esin; İrem Bilgetekin; Umut Demirci; Çağlar Köseoğlu; Alper Topal; Nuri Karadurmuş; Haktan Bağış Erdem; Taha Bahsi

doi:10.1016/j.mrfmmm.2023.111831

Uncommon variants detected via hereditary cancer panel and suggestions for genetic counseling

Mutat Res. 2023 Jul-Dec:827:111831. doi: 10.1016/j.mrfmmm.2023.111831. Epub 2023 Jul 4.

Authors

Affiliations

¹ Ankara Etlik City Hospital, Department of Medical Genetics, Ankara, Turkiye. Electronic address: zeynepozdemirmd@gmail.com.
² Ankara Etlik City Hospital, Department of Medical Genetics, Ankara, Turkiye.
³ Ankara Etlik City Hospital, Department of Medical Oncology, Ankara, Turkiye.
⁴ University of Health Sciences, Ankara Oncology Training and Research Hospital, Department of Medical Oncology, Ankara, Turkiye.
⁵ Bayındır Hospital, Department of Medical Oncology, Ankara, Turkiye.
⁶ Lösante Hospital, Department of Medical Oncology, Ankara, Türkiye.
⁷ Memorial Hospital, Department of Medical Oncology, Ankara, Turkiye.
⁸ University of Health Sciences, Gülhane Training and Research Hospital, Department of Medical Oncology, Ankara, Turkiye.

PMID: 37453313
DOI: 10.1016/j.mrfmmm.2023.111831

Abstract

Objective: Hereditary cancer syndromes constitute 5-10% of all cancers. The development of next-generation sequencing technologies has made it possible to examine many hereditary cancer syndrome-causing genes in a single panel. This study's goal was to describe the prevalence and the variant spectrum using NGS in individuals who were thought to have a hereditary predisposition for cancer.

Material and method: Analysis was performed for 1254 who were thought to have a familial predisposition for cancer. We excluded 46 patients who were carrying BRCA1/2 variants in this study, for focusing on the rare gene mutations. Sequencing was performed using the Sophia Hereditary Cancer Solution v1.1 Panel and the Qiagen Large Hereditary Cancer Panel. The Illumina MiSeq system was used for the sequencing procedure. The software used for the data analyses was Sophia DDM and QIAGEN Clinical Insight (QCITM) Analyze. The resulting genomic changes were classified according to the current guidelines of ACMG/AMP.

Results: Pathogenic/likely pathogenic variants were detected in 172 (13.7%) of 1254 patients. After excluding the 46 BRCA1/2-positive patients, among the remaining 126 patients; there were 60 (4.8%) breast cancer, 33 (2.6%) colorectal cancer, 9 (0.7%) ovarian cancer, 5 (0.4%) endometrium cancer, 5 (0.4%) stomach cancer, 3 (0.2%) prostate cancer patients. The most altered genes were MUTYH in 27 (2.1%) patients, MMR genes (MLH1, MSH6, MSH, MSH2, PMS2 and EPCAM) in 26 (2%) patients, and ATM in 25 (2%) patients. We also examined the genotype-phenotype correlation in rare variants. Additionally, we identified 11 novel variations.

Conclusion: This study provided significant information regarding rare variants observed in the Turkish population because it was carried out with a large patient group. Personalized treatment options and genetic counseling for the patients are therefore made facilitated.

Keywords: Hereditary cancer syndromes; Multigene panel testing; Next generation sequencing.

MeSH terms

BRCA1 Protein* / genetics
BRCA2 Protein / genetics
Breast Neoplasms* / genetics
Female
Genetic Counseling
Genetic Predisposition to Disease
Germ-Line Mutation
Humans
Male

Substances

BRCA1 protein, human
BRCA1 Protein
BRCA2 protein, human
BRCA2 Protein