Whole-exome sequencing reveals an association of rs112065068 in TGOLN2 gene with distant metastasis of non-small cell lung cancer

Tatiana Gerashchenko; Rostislav Skitchenko; Anastasia Korobeynikova; Kristina Kuanysheva; Anna Khozyainova; Rostislav Vorobiev; Evgeny Rodionov; Sergey Miller; Evgeny Topolnitsky; Nikolay Shefer; Maxim Anisimenko; Lilia Zhuikova; Mrinal Vashisth; Olga Pankova; Vladimir Perelmuter; Valeria Rezapova; Mykyta Artomov; Evgeny Denisov

doi:10.1016/j.gene.2024.148507

Whole-exome sequencing reveals an association of rs112065068 in TGOLN2 gene with distant metastasis of non-small cell lung cancer

Gene. 2024 Apr 24:920:148507. doi: 10.1016/j.gene.2024.148507. Online ahead of print.

Authors

Tatiana Gerashchenko¹, Rostislav Skitchenko², Anastasia Korobeynikova¹, Kristina Kuanysheva³, Anna Khozyainova³, Rostislav Vorobiev³, Evgeny Rodionov⁴, Sergey Miller⁴, Evgeny Topolnitsky⁵, Nikolay Shefer⁵, Maxim Anisimenko⁶, Lilia Zhuikova⁷, Mrinal Vashisth⁸, Olga Pankova⁹, Vladimir Perelmuter⁹, Valeria Rezapova¹⁰, Mykyta Artomov¹¹, Evgeny Denisov¹²

Affiliations

¹ Laboratory of Cancer Progression Biology, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Kooperativny Str. 5, Tomsk 634009, Russia; Laboratory of Single Cell Biology, Research Institute of Molecular and Cellular Medicine, Peoples' Friendship University of Russia (RUDN University), Miklukho-Maklaya Str. 6, Moscow 117198, Russia.
² ITMO, Kronverksky Pr. 49, Bldg. A, St. Petersburg, 197101, Russia.
³ Laboratory of Cancer Progression Biology, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Kooperativny Str. 5, Tomsk 634009, Russia.
⁴ Department of Thoracic Oncology, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Kooperativny Str. 5, Tomsk 634009, Russia.
⁵ Department of Surgery with a Course of Mobilization Training and Disaster Medicine, Siberian State Medical University, Moskovskiy Tract 2, Tomsk 634050, Russia.
⁶ Federal Research Center Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Ac. Lavrentieva Ave. 10, Novosibirsk 630090, Russia.
⁷ Laboratory of Epidemiology, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Kooperativny Str. 5, Tomsk 634009, Russia.
⁸ Tomsk State University, Lenina Ave. 36, Tomsk 634050, Russia.
⁹ Department of General and Molecular Pathology, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Kooperativny Str. 5, Tomsk 634009, Russia.
¹⁰ ITMO, Kronverksky Pr. 49, Bldg. A, St. Petersburg, 197101, Russia; University Cote D'Azur, Grand Château 28 Avenue de Valrose, Nice 06103, France.
¹¹ The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH 43205, USA; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43215, USA.
¹² Laboratory of Cancer Progression Biology, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Kooperativny Str. 5, Tomsk 634009, Russia; Laboratory of Single Cell Biology, Research Institute of Molecular and Cellular Medicine, Peoples' Friendship University of Russia (RUDN University), Miklukho-Maklaya Str. 6, Moscow 117198, Russia. Electronic address: d_evgeniy@oncology.tomsk.ru.

PMID: 38670394
DOI: 10.1016/j.gene.2024.148507

Abstract

Early prediction and prevention of recurring illness is critical for improving the survival rates of patients with non-small cell lung cancer (NSCLC). Previously, we demonstrated that the presence of premalignant epithelial changes in the small bronchi distant to the primary tumor is associated with NSCLC progression: isolated basal cell hyperplasia (iBCH) indicates a high risk of distant metastasis, BCH combined with squamous metaplasia (BCH^SM) - a high risk of locoregional recurrence. Here, we aimed to identify germline single nucleotide variants (SNVs) and insertions and deletions (InDels) associated with distant metastasis and locoregional recurrence in cases with iBCH and BCH^SM using whole-exome sequencing of 172 NSCLC patients. The rs112065068 of the TGOLN2 gene was identified only in iBCH patients and was associated with a high risk of distant metastasis (P < .001) and worse metastasis-free survival (HR = 4.19 (95 %CI 1.97-8.93); P < .001). This variant was validated in a group of 109 NSCLC patients using real-time PCR and Sanger sequencing analyses. To our knowledge, this study is the first to identify a germline variant associated with NSCLC distant metastasis.

Keywords: Genetic predisposition; Germline variant; Lung cancer; Metastasis; Premalignant lesions; Whole-exome sequencing.