Maaia Margo Jentus, Leontine Bakker, Marco Verstegen, Iris Pelsma, Tom van Wezel, Dina Ruano, Ellen Kapiteijn, Stijn Crobach, Nienke Biermasz, Hans Morreau
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We identified four distinct chromosomal patterns, with varying distribution among different tumor lineages. Forty-two of 61 (69%) PitNETs showed chromosomal alterations. Gonadotroph PitNETs showed mostly quiet genomes. The majority of lactotroph PitNETs (19/20, 95%) were altered, exhibiting a gained genome and a remarkably low recurrence rate. Nine of ten (90%) corticotroph PitNETs harbored chromosomal alterations, of which two aggressive corticotroph tumors and one metastatic corticotroph PitNET showed massive chromosomal losses, leading to near-haploid/near-homozygous genomes. The comparison of the molecular profile of primary and recurrent PitNETs of five patients showed no significant accumulation of alterations over time. A simple genome-wide 1500-SNP test can be used in the identification of outspoken aggressive subsets of PitNETs by the occurrence of a near-haploid/near-homozygous genome. Furthermore, the presence of neoplastic tissue in the resected material can be potentially confirmed for non-gonadotroph PitNETs under suboptimal histological assessment conditions.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Chromosomal alteration patterns in PitNETs: massive losses in aggressive tumors.\",\"authors\":\"Maaia Margo Jentus, Leontine Bakker, Marco Verstegen, Iris Pelsma, Tom van Wezel, Dina Ruano, Ellen Kapiteijn, Stijn Crobach, Nienke Biermasz, Hans Morreau\",\"doi\":\"10.1530/ERC-24-0070\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The molecular biology of pituitary neuroendocrine tumors (PitNETs) revealed few recurrent mutations and extensive chromosomal alterations, with the latter being the driving force in a subset of these lesions. 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Nine of ten (90%) corticotroph PitNETs harbored chromosomal alterations, of which two aggressive corticotroph tumors and one metastatic corticotroph PitNET showed massive chromosomal losses, leading to near-haploid/near-homozygous genomes. The comparison of the molecular profile of primary and recurrent PitNETs of five patients showed no significant accumulation of alterations over time. A simple genome-wide 1500-SNP test can be used in the identification of outspoken aggressive subsets of PitNETs by the occurrence of a near-haploid/near-homozygous genome. 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引用次数: 0
摘要
垂体神经内分泌肿瘤(PitNETs)的分子生物学研究发现,复发性突变很少,而染色体改变却很广泛,后者是这些病变中一部分的驱动力。为了满足对易于应用的诊断工具的需求,我们对在一家三级医疗中心手术的 61 例 PitNET 进行了回顾性研究。所有病例都根据 2022 年世界卫生组织内分泌肿瘤分类进行了亚型划分。研究人员利用针对 1500 个单核苷酸多态性(SNP)的全基因组 NGS 面板对福尔马林固定石蜡包埋组织 DNA 中的染色体失衡、杂合性缺失和拷贝数变异进行了分类。我们发现了四种不同的染色体模式,它们在不同肿瘤系中的分布各不相同。61例PitNET中有42例(69%)出现染色体改变。促性腺激素型PitNET的基因组大多是安静的。大多数泌乳型PitNET(19/20,95%)的基因组发生了改变,表现为基因组增殖,且复发率极低。10个皮质营养型PitNET中有9个(90%)存在染色体改变,其中2个侵袭性皮质营养型肿瘤和1个转移性皮质营养型PitNET出现大量染色体缺失,导致近单倍体/近同源基因组。对五名患者的原发性和复发性 PitNET 的分子图谱进行比较后发现,随着时间的推移,这些改变并没有明显的累积。一个简单的全基因组 1500 SNP 检测可用于通过近单倍体/近同源基因组的出现来鉴别 PitNET 的明显侵袭性亚群。此外,在组织学评估条件不理想的情况下,切除材料中是否存在肿瘤组织也有可能被确认为非促性腺激素PitNET。
Chromosomal alteration patterns in PitNETs: massive losses in aggressive tumors.
The molecular biology of pituitary neuroendocrine tumors (PitNETs) revealed few recurrent mutations and extensive chromosomal alterations, with the latter being the driving force in a subset of these lesions. Addressing the need for an easily applicable diagnostic tool, we conducted a retrospective study of 61 PitNETs operated at a tertiary care center. All cases were subtyped according to the 2022 WHO Classification of Endocrine Tumors. A genome-wide next-generation sequencing panel targeting 1500 single nucleotide polymorphisms (SNPs) was used to classify chromosomal imbalances, loss of heterozygosity, and copy number variations in DNA from formalin-fixed paraffin-embedded tissues. We identified four distinct chromosomal patterns, with varying distribution among different tumor lineages. Forty-two of 61 (69%) PitNETs showed chromosomal alterations. Gonadotroph PitNETs showed mostly quiet genomes. The majority of lactotroph PitNETs (19/20, 95%) were altered, exhibiting a gained genome and a remarkably low recurrence rate. Nine of ten (90%) corticotroph PitNETs harbored chromosomal alterations, of which two aggressive corticotroph tumors and one metastatic corticotroph PitNET showed massive chromosomal losses, leading to near-haploid/near-homozygous genomes. The comparison of the molecular profile of primary and recurrent PitNETs of five patients showed no significant accumulation of alterations over time. A simple genome-wide 1500-SNP test can be used in the identification of outspoken aggressive subsets of PitNETs by the occurrence of a near-haploid/near-homozygous genome. Furthermore, the presence of neoplastic tissue in the resected material can be potentially confirmed for non-gonadotroph PitNETs under suboptimal histological assessment conditions.