<abstract xmlns="http://www.w3.org/1999/xhtml">

<sec id="j_raon-2023-0013_s_006"><h3>Background</h3>
<p>Thymomas belong to rare tumors giving rise to thymic epithelial tissue. There is a classification of several forms of thymoma: A, AB, B1, B2, B3, thymic carcinoma (TC) and thymic neuroendocrine thymoma. In this meta-analysis study, we have focused on thymoma using articles based on the disease’s next-generation sequencing (NGS) genomic profiling.</p></sec>
<sec id="j_raon-2023-0013_s_007"><h3>Materials and methods</h3>
<p>We conducted a systematic review and meta-analysis of the prevalence of studies that discovered the genes and variants occurring in the less aggressive forms of the thymic epithelial tumors. Studies published before 12<sup>th</sup> December 2022 were identified through PubMed, Web of Science (WoS), and SCOPUS databases. Two reviewers have searched for the bases and selected the articles for the final analysis, based on well-defined exclusion and inclusion criteria.</p></sec>
<sec id="j_raon-2023-0013_s_008"><h3>Results</h3>
<p>Finally, 12 publications were included in the qualitative as well as quantitative analysis. The three genes, <italic>GTF2I</italic>, <italic>TP53</italic>, and <italic>HRAS</italic>, emerged as disease-significant in the observed studies. The Odds Ratio for all three extracted genes <italic>GTF2I</italic> (OR = 1.58, CI [1.51, 1.66] p &lt; 0.00001)<italic>, TP53</italic> (OR = 1.36, CI [1.12, 1.65], p &lt; 0.002), and <italic>HRAS</italic> (OR = 1.02, CI [1.00, 1.04], p &lt; 0.001).</p></sec>
<sec id="j_raon-2023-0013_s_009"><h3>Conclusions</h3>
<p>According to obtained data, we noticed that the <italic>GTF2I</italic> gene exhibits a significant prevalence in the cohort of observed thymoma patients. Moreover, analyzing published articles NGS has suggested <italic>GTF2I, TP53</italic>, and <italic>HRAS</italic> genes as the most frequently mutated genes in thymoma that have pathogenic single nucleotide variants (SNV) and Insertion/Deletion (InDel), which contribute to disease development and progression. These variants could be valuable biomarkers and target points specific to thymoma.</p></sec>
</abstract>

Background
Thymomas belong to rare tumors giving rise to thymic epithelial tissue. There is a classification of several forms of thymoma: A, AB, B1, B2, B3, thymic carcinoma (TC) and thymic neuroendocrine thymoma. In this meta-analysis study, we have focused on thymoma using articles based on the disease’s next-generation sequencing (NGS) genomic profiling.
Materials and methods
We conducted a systematic review and meta-analysis of the prevalence of studies that discovered the genes and variants occurring in the less aggressive forms of the thymic epithelial tumors. Studies published before 12th December 2022 were identified through PubMed, Web of Science (WoS), and SCOPUS databases. Two reviewers have searched for the bases and selected the articles for the final analysis, based on well-defined exclusion and inclusion criteria.
Results
Finally, 12 publications were included in the qualitative as well as quantitative analysis. The three genes, GTF2I, TP53, and HRAS, emerged as disease-significant in the observed studies. The Odds Ratio for all three extracted genes GTF2I (OR = 1.58, CI [1.51, 1.66] p < 0.00001), TP53 (OR = 1.36, CI [1.12, 1.65], p < 0.002), and HRAS (OR = 1.02, CI [1.00, 1.04], p < 0.001).
Conclusions
According to obtained data, we noticed that the GTF2I gene exhibits a significant prevalence in the cohort of observed thymoma patients. Moreover, analyzing published articles NGS has suggested GTF2I, TP53, and HRAS genes as the most frequently mutated genes in thymoma that have pathogenic single nucleotide variants (SNV) and Insertion/Deletion (InDel), which contribute to disease development and progression. These variants could be valuable biomarkers and target points specific to thymoma.

Molecular profiling of rare thymoma using next-generation sequencing: meta-analysis

Radiology and Oncology

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Background
Thymomas belong to rare tumors giving rise to thymic epithelial tissue. There is a classification of several forms of thymoma: A, AB, B1, B2, B3,...

Author	Year	Study design	Thymoma	Gene (SNV)	Number of cases	number Total of cases	NGS genomics
				APC	23
				TP53	12
				ATM	22
Chen K, China	2020	Cross-sectional	Type A, AB, B1, B2, B3	AKT1	5	50	TS
				SMAD4	12
				ALK	19
				KRAS	2
				NRAS	2
				HRAS	3
Enkner F, Austria	2017	Cross-sectional	Type A, B	SMARCB1	1	19	TS
				STK11	1
Higuchi R, Japan	2020	Cross-sectional	Type A, AB, B	GTF2I	14	22	TS
Petrini I, Italia	2014	Cross-sectional	Type A, AB	GTF2I	119	270	ES
				GTF2I	44
Radovich M, USA	2017	Case-control	Type A, AB	HRAS	10	105	MOPA
				TP53	2
				HRAS	1
				PIK3CA	2		SNaPshot
Sakane T, Japan	2020	Cross-sectional	Type A, B2, B3, B4, B5	AKT1	1	33
				RAS pathway	1		Multiplex
				EGFR pathway	3
Song ZB, China	2016		Type B2, B3	PIK3CA	1	37	TS
				EGFR	1		IonAmpliSeq
				SMAD4	27
				APC	27
Peric J, Serbia	2020	Case-control	Type A, B1, B2, B3	ATM	26	35	TSACP
				ERBB4	24
				TP53	26
Xu S, China	2021	Cross-sectional	Type A, AB B1, B2, B3	TP53	9	17	ES
				HRAS	2
Liang N, China	2021	Cross-sectional	Type A, AB, B1, B2, B3	GTF2I	15	24	SureSelectXT TS
Szpechcinski A, Poland	2022	Cross-sectional	Type B2B3	ERBBKIT 2	11	19	TS
				KIT	1
Girard N, France	2022	Cross-sectional	Type A, B1, B2, B3	TPHRAS 53	81	90	WES
				Other genes	80

Molecular profiling of rare thymoma using next-generation sequencing: meta-analysis

Article Category: Review

Published Online: Mar 22, 2023

Page range: 12 - 19

Received: Oct 21, 2022

Accepted: Jan 31, 2023

DOI: https://doi.org/10.2478/raon-2023-0013

© 2023 Jelena Kostic Peric, Andja Cirkovic, Sanja Srzentic Drazilov, Natalija Samardzic, Vesna Skodric Trifunovic, Dragana Jovanovic, Sonja Pavlovic, published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

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Characteristics of 12 selected studies