ETA2023 45th Annual Meeting of the European Thyroid Association ETA 2023 Oral Session 12: Emerging Insights into Thyroid Cancer Genetics (5 abstracts)
Comparative analysis of somatic copy number alterations (SCNA) between hürthle cell tumors (HCT) and oncocytic variant of follicular cell derived thyroid tumors (OV-FCDTT)
Sule Canberk 1 , Marta Ferreira 2 , Carla Oliveira 3 , Joana Reis 4 , Rita Barros 5 , Luisa Pereira 6 , Hugo Osório 7 , Elisabete Rios 8 , Arnaud Paula 9 , Paula Soares 10 & Valdemar Maximo 11
1Ipatimup/I3s - Instituto de Investigação e Inovação Em Saúde Da Universidade Do Porto, Cancer Signalling and Metabolism Research Group, Pathology, Porto, Portugal; 2Instituto de Investigação e Inovação Em Saúde Da Universidade Do Porto, I3s - Instituto de Investigação e Inovação Em Saúde Da Universidade Do Porto, Expression Regulation in Cancer Research Group, Porto, Portugal; 3I3s - Instituto de Investigação e Inovação Em Saúde, Universidade Do Porto, Expression Regulation in Cancer, Expression Regulation in Cancer Research Group, Porto, Portugal; 4I3s, Instituto de Investigação e Inovação Em Saúde, University of Porto, 4200-135 Porto, Portugal., Portugal; 5Instituto de Investigação e Inovação Em Saúde Da Universidade Do Porto, Intercellular Communication and Cancer Research Group, Portugal; 6Instituto de Investigação e Inovação Em Saúde Da Universidade Do Porto, Genetic Diversity Research Group, Porto, Portugal; 7I3s - Instituto de Investigação e Inovação Em Saúde Da Universidade Do Porto, Portugal; 8Centro Hospitalar São João, University of Porto, Anatomia Patológica, Portugal; 9I3s - Instituto de Investigação e Inovação Em Saúde Da Universidade Do Porto, Cancer Signalling and Metabolism, Portugal; 10Medical Faculty University of Porto, Ipatimup, Cancer Signaling and Metabolism Group, Porto, Portugal; 11Department of Pathology of Medical Faculty of University of Porto, Instituto de Investigação e Inovação Em Saúde Da Universidade Do Porto, Cancer Signalling and Metabolism Research Group, Porto, Portugal
Objectives: Somatic copy number alterations (SCNAs) have been the most common genetic alterations identified in cancer, that frequently related with extensive genomic instability and to an aggressive behavior. Hürthle cell carcinoma is known to be aggressive, having the highest incidence of recurrences, distant metastasis and RAI therapy resistance among all differentiated follicular cell derived thyroid carcinomas. Due to these differences and recent molecular discoveries, Hurtle cell tumors (HCTs) have been defined and characterized as a separate histological subtype among follicular cell derived thyroid carcinomas in the 4th WHO endocrine blue book edition. Until this last classification, HCTs were considered as subtypes of follicular thyroid tumors. For that reason, most of the previous studies on SCNAs include both the HCTs and other thyroid tumors presenting some level of oncocytic morphology, the oncocytic variant of other follicular cell derived thyroid tumours AKA mitochondrion-rich non-Hürthle thyroid tumours (OV-FCDTTs). Hence, to better understand the genomic instability affecting HCTs, we conducted a SCNA analysis comparing HCTs vs OV-FCDTTs separately.
Methods: DNA extracted from 12 HCTs and 6 OV-FCDTTs was submitted to shallow whole-genome sequencing (sWGS). Sequencing reads were aligned to the reference human genome (GRCh37) using the Burrows-Wheeler Aligner (BWA v0.7.15). Copy number alterations (meaning, copy number gains and losses, gene amplifications and homozygous deletions) were determined using QDNAseq by deriving the Log2 ratio values across all genomic regions of the tumor samples from the Log2 values taken from a normal reference.
Results: HCTs had more SCNAs than OV-FCDTTs, including copy number losses of chromosomes 9q and 22q (n =5/12, 42% for both), and gains of chromosomes 19 (n =7/12, 58%) and 20q, (n =6/12, 50%). In addition, we identified 42 genes that were found to present amplification (n =36) or deletion (n =6) in HCTs. From the 36 amplified genes, 7 were found to be recurrently affected (UBR3, SLC9A9, SEC63, GRIA2, FER, FRS2 and NELL2), and from the 6 deleted genes, 2 of them were seen to be recurrently affected in HCTs (SLC25A46, ACSS3). In OV-FCDTTs, only 5 genes were found to be amplified (n =3) or deleted (n =2) with only 2 genes being recurrently amplified (SOX14 and TIPARP).
Conclusions: We found that HCTs have a higher genomic instability, when compared to OV-FCDTTs, has verified by the frequent occurrence of SCNA. Additional studies are warranted to better elucidate if the genetic instability detected in HTC’s is associated with the prognosis features of those tumours.
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Endocrine Abstracts
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