Endocrine-related cancer最新文献

{"title":"Efficacy and safety of RET-kinase inhibitors in RET-altered thyroid cancers: a systematic review and single-arm meta-analysis.","authors":"Israt Jahan Riya, Ifrat Jahan Piya, Jonathan N Priantti, Cha Len Lee, Lina Barman, Almunthir Altobi","doi":"10.1530/ERC-24-0219","DOIUrl":"10.1530/ERC-24-0219","url":null,"abstract":"<p><p>The RET proto-oncogene, which encodes a receptor tyrosine kinase, is an important factor in the pathogenesis of medullary and papillary thyroid cancers. Selpercatinib and pralsetinib, both specific RET-kinase inhibitors, are the only FDA-approved drugs for treating RET-altered thyroid cancer. We wanted to evaluate the safety and efficacy of selpercatinib and pralsetinib in RET-altered thyroid cancers. We searched the PubMed, Embase, Cochrane, and Clinicaltrials.gov databases for randomized controlled trials and observational studies published up to March 30, 2024, and included those that reported any of the desired endpoints. The primary endpoints were 1-year progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Quantitative analyses were performed using the R programming language. We included four studies with 560 patients, 510 with RET-mutant and 50 with RET-fusion thyroid cancer. The 1-year PFS was 84% (95% CI, 79-88, I 2 = 43%), ORR was 69% (95% CI, 65-73, I 2 = 0) and DCR was 93% (95% CI, 89-96, I 2 = 44%). Some important grade ≥3 adverse events were hypertension (16%; 95% CI, 11-22; I 2 = 43%), diarrhea (3%; 95% CI, 2-5; I 2 = 0), increased ALT (11%; 95% CI, 8-14; I 2 = 0) and increased AST (6%; 95% CI, 4-10; I 2 = 0). In conclusion, these findings suggest that selpercatinib and pralsetinib are efficacious and safe for use in patients with RET-altered thyroid cancer.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144046315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ERRATUM: Roles of the HOXA10 gene during castrate-resistant prostate cancer progression.","authors":"Zhi Long, Yinan Li, Yu Gan, Dongyu Zhao, Guangyu Wang, Ning Xie, Jessica M Lovnicki, Ladan Fazli, Qi Cao, Kaifu Chen, Xuesen Dong","doi":"10.1530/ERC-18-0465e","DOIUrl":"10.1530/ERC-18-0465e","url":null,"abstract":"","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":"32 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo and in vitro analysis of functional effects of the SDHD H50R variant.","authors":"Shivam Priya, Karthik Chakravarthy, Edward Ziegler, Xavier Vesco, Krista La Perle, Xiaoli Zhang, Lawrence S Kirschner","doi":"10.1530/ERC-24-0337","DOIUrl":"10.1530/ERC-24-0337","url":null,"abstract":"<p><p>Germline mutations in the four genes (SDHA, SDHB, SDHC and SDHD) encoding the succinate dehydrogenase (SDH) holoenzyme are known to predispose towards the development of tumor including pheochromocytomas/paragangliomas (PPGLs), gastrointestinal stromal tumors (GISTs), clear cell renal cancers (RCC) and possibly others. Mutations in these genes have also been described in patients with Cowden syndrome, which includes tumors of the breast, brain and thyroid gland. Although nonsense mutations are clearly pathogenic, the functional consequences of many missense mutations are unclear. It has previously been reported that the missense mutations SDHDG12S and SDHDH50R predispose to thyroid and breast cancers, although this characterization has been disputed. To address this question, we developed mouse models to test tumorigenicity of these variants. The reference mouse genome codes for a serine at residue 12 in Sdhd, so this variant was not pursued further. To assess the role of SDHDH50R (H50R), we generated a knock-in mouse allele for this variant and studied its effects in vivo as well as in vitro in mouse embryonic fibroblasts. Unlike null alleles for Sdhd, the H50R allele did not produce embryonic lethality when homozygous. There was no statistically significant difference in survival or tumor formation in homozygous or heterozygous animals compared to littermate controls. In vitro studies similarly failed to detect significant differences in proliferation, colony formation or metabolic function. Based on our analysis of this allele's function both in vivo and in vitro, we conclude that the SDHDH50R allele is most likely a non-pathogenic polymorphism.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinicopathological characteristics associated with the prognosis of recurrent gonadotroph tumors.","authors":"Chrysi Kaparounaki, Alexandre Vasiljevic, Emmanuel Jouanneau, Camille Sergeant, Gérald Raverot, Mirela-Diana Ilie","doi":"10.1530/ERC-24-0186","DOIUrl":"10.1530/ERC-24-0186","url":null,"abstract":"<p><p>Although gonadotroph tumor regrowth is frequent after pituitary surgery, the systematic use of adjuvant radiotherapy is limited by its long-term complications. In this context, it is important to predict which tumors are most likely to regrow after surgery, and especially, which tumors are most likely to regrow rapidly. Clinicopathological characteristics associated with the prognosis of radiotherapy-naïve, recurrent pituitary tumors are currently unknown. In this longitudinal, observational, retrospective, monocentric cohort study, we analyzed the clinicopathological characteristics associated with the prognosis of recurrent, radiotherapy-naïve gonadotroph tumors, specifically with the progression-free survival after a second pituitary surgery. We found that the Ki67 index of radiotherapy-naïve, recurrent gonadotroph tumors was the only parameter statistically associated with the progression-free survival after a second pituitary surgery, P = 0.02. Specifically, radiotherapy-naïve gonadotroph tumors with a positive Ki67 index had shorter progression-free survival after the second surgery (median 31 months) compared to radiotherapy-naïve gonadotroph tumors with a negative Ki67 index (median 75 months). Thus, our study pinpoints that the Ki67 index could be used to guide the management strategy for recurrent gonadotroph tumors that are still radiotherapy-naïve by the time of the second pituitary surgery.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144055956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surrogate molecular classification of LAR breast cancer in routine workflow.","authors":"Nelson Rangel, Laura Serrao, Giulia Capella, Giulia Orlando, Federica Ragno, Milena Rondón-Lagos, Jasna Metovic, Paola Cassoni, Isabella Castellano","doi":"10.1530/ERC-24-0316","DOIUrl":"10.1530/ERC-24-0316","url":null,"abstract":"<p><p>Triple negative breast cancer (TNBC) is a heterogeneous disease, considered the most aggressive among all diagnosed breast cancers. The luminal androgen receptor (LAR) category has been recognized as a distinct entity (subtype), observed in around 15% of the TNBCs, but currently there is no complete overlap to clearly distinguish them from the other TNBC counterparts. With the aim to better establish morphological, immunohistochemical and molecular features of LAR tumors, gene and signatures expression was evaluated in 42 well-characterized TNBCs. Furthermore, protein expression of a panel of several markers (AR, FOXA1, CK5/6, p63, GCDFP-15 and FGFR4) was also studied. Compared with non-LAR cases, LAR tumors often display low tumor grade, reduced levels of Ki-67, total absence of CK5/6 and p63 basal markers expression, but show high positivity for AR, FOXA1 and FGFR4. Regarding molecular assessment, LAR tumors were characterized by higher scores of gene signatures associated with AR, FOXA1 and ERBB2, while showed lower scores of signatures related to BC proliferation, CDK6, BRCAness and p53. Our results suggest that among TNBC, LAR cases are associated with features indicative of a less aggressive tumor behavior. Accurate distinction of this TNBC subtype is important since they are resistant to chemotherapy and may potentially benefit from tailored-therapeutical approaches. Specifically, therapies targeting AR together to additional proteins, such as FGFR4, FOXA1 or CDK6, may represent future directions in the treatment approach of LAR tumors.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":"32 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genotype-specific neoplastic risk profiles in patients with VHL disease.","authors":"Athina Ganner, Alfonso Massimiliano Ferrara, Peggy Sekula, Francesca Schiavi, Julia H Joo, Gabriela Sanso, Madson Q Almeida, Anna Laura Knoblauch, Christine Julia Gizaw, Karol Krzystolik, Sophie Charlotte Astheimer, Maria Isabel Achatz, Ana Vieites, Diane Donegan, Thomas Hundsberger, Jan Lubinski, Ilgin Yildirim Simsir, Tushar Bandgar, Kornelia Hasse-Lazar, Agnieszka Pawlaczek, Wouter Zandee, Kai Yu, Claudio E Kater, Liliya Rostomyan, Xiao-Ping Qi, Timo Deutschbein, Hanna Remde, Tabatha Nakakogue Dallagnol, Marina Yukina, Rene Baudrand, Corina E Andreescu, Tada Kunavisarut, Nur Diana Ishak, Xavier Le Guillou Horn, Gemma Shutler, Milan Jovanovic, Mariola Pęczkowska, Jan Calissendorff, Francesco Circosta, Maria João Bugalho, Eleonora P M Corssmit, Oliver Gimm, Marcus Quinkler, Andrea Goldmann, Sara Watutantrige Fernando, Stefania Zovato, Lucas S Santana, Felipe Freitas-Castro, Christian Rothermundt, Josa Zimmermann, Asude Durmaz, Ayca Aykut, Laurent Vroonen, Tobias Krauss, Christian Taschner, Juri Ruf, Jan-Helge Klingler, Sven Gläsker, Stefan Lang, Felicitas Bucher, Hansjürgen Agostini, Cordula Jilg, Wolfgang Schultze-Seemann, Birke Bausch, Antonia Bergfeld, Kilian Rhein, Thomas Uslar, Antonio Concistrè, C Christofer Juhlin, José Cláudio Casali-da-Rocha, Luigi Petramala, Uliana Tsoy, Elena Grineva, Xu-Dong Fang, Fruzsina Kotsis, Tobias Schaefer, Thera P Links, Özer Makay, Gustavo F C Fagundes, Joanne Ngeow, Nalini Shah, Giuseppe Opocher, Marta Barontini, Catharina Larsson, Andrzej Januszewicz, José Viana Lima, Nelson Wohllk, Claudio Letizia, Gianluca Donatini, Eamonn R Maher, Dmitry Beltsevich, Irina Bancos, Cezary Cybulski, Martin K Walz, Anna Köttgen, Charis Eng, Hartmut P H Neumann, Elke Neumann-Haefelin","doi":"10.1530/ERC-24-0260","DOIUrl":"10.1530/ERC-24-0260","url":null,"abstract":"<p><p>Hereditary tumor predisposition syndromes pose a challenge for early detection and timely treatment of tumors. In von Hippel-Lindau disease, desirable personalized surveillance programs are lacking due to insufficient data on genotype-specific risk profiles of individual mutations. To describe neoplastic risk profiles for carriers of pathogenic and likely pathogenic VHL germline mutations, our observational study recruited 1,350 participants from 40 centers worldwide. 432 different VHL germline mutations were observed, with p.Asn78Ser, p.Arg161Ter, p.Arg161Gln, p.Arg167Gln, p.Arg167Trp and p.Tyr98His being the six most frequent, occurring in a total of 493 carriers (36.5%) and in ≥30 patients each. Age-related penetrance risks for retinal hemangioblastoma, central nervous system hemangioblastoma, renal cell carcinoma, pancreatic neuroendocrine tumors and pheochromocytoma/paraganglioma in carriers of the most frequent VHL mutations were assessed. In addition, the number of organs affected, the frequency of surgery and the outcome are reported. Pairwise comparisons of the age-dependent tumor penetrance of these six mutations showed that 47 out of 90 pairs were significantly different. The most significant associations were found in p.Tyr98His (n = 19), followed by p.Arg161Ter (n = 10). All pairwise comparisons of mutations affecting different codons showed at least one significant (P < 0.05) difference, except for p.Asn78Ser vs p.Arg161Ter. Thus, tumor risk varied by VHL mutation type and location, but did not differ between the truncating mutation p.Arg161Ter and the missense mutation p.Asn78Ser. Our study demonstrates the importance of mutation-specific phenotype prediction. With appropriate validation, the data have important implications for risk assessment and decision making in tumor prevention for carriers of the respective VHL mutations.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":"32 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12060576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144061044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spanish consensus on the diagnosis and management of adrenocortical carcinoma.","authors":"Marta Araujo-Castro, Cristina Álvarez-Escola, Ana Casteràs, Alberto Carmona-Bayonas, María-Dolores Chiara, Felicia A Hanzu, Jorge Hernando, José L Vercher-Conejero, Macarena Rodríguez-Fraile, Victoria Gómez Dos Santos, Paula Jimenez-Fonseca, Alexandra Giraldo, Nuria Valdés, Oscar Vidal, Maribel Del Olmo-García, Jaume Capdevila","doi":"10.1530/ERC-25-0034","DOIUrl":"https://doi.org/10.1530/ERC-25-0034","url":null,"abstract":"<p><p>Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with an estimated incidence of 0.7-2 cases per million/year. The rarity of this disease, coupled with limited preclinical models and clinical trials, has hindered progress, resulting in poor outcomes, with a 5-year survival rate of approximately 35%. Currently, the only available curative treatment is complete surgical resection of the adrenal tumor. For unresectable or metastatic ACC, the current standard therapeutic modalities are mitotane, chemotherapy, radiotherapy and locoregional treatments; however, these are noncurative. Mitotane has an adrenolytic and anti-steroidogenic effect, and it is used in the adjuvant setting for high-risk patients, as systemic therapy for metastatic disease, and/or to control hormonal secretion. While key pathways in ACC pathogenesis have been identified as potential therapeutic targets, results with targeted therapies remain modest, showing that there is a clinical unmet need for novel treatments or new combinations of exiting drugs. Effective management requires a multidisciplinary team of experts to optimize outcomes for patients. This article presents a multidisciplinary consensus on the diagnosis, management, prognosis and follow-up of patients with ACC, and the approach to two special contexts, ACC in pregnant women and hormone-producing ACC. The consensus was coordinated by the Spanish Society of Endocrinology and Nutrition (SEEN) and the Spanish Group of Neuroendocrine and Endocrine Tumors (GETNE), with contribution from experts from related societies including the Spanish Association of Surgeons (AEC), Spanish Society of Urology (AEU), Anatomic-Pathology (SEAP), Nuclear Medicine (SEMNIM), Medical Oncology (SEOM) and Radiotherapeutic Oncology (SEOR).</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":"32 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12053981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From bench to bedside in the sella: translational developments in pituitary tumour genetics.","authors":"Sunita M C De Sousa","doi":"10.1530/ERC-24-0272","DOIUrl":"10.1530/ERC-24-0272","url":null,"abstract":"<p><p>The two most prevalent pituitary tumour types are pituitary adenomas (also referred to as pituitary neuroendocrine tumours or pitNETs) and craniopharyngiomas, collectively accounting for 98% of all pituitary tumours. The genetic basis of these pituitary tumours is partly understood. In pituitary adenomas, established predisposition genes in the germline setting are MEN1, PRKAR1A, AIP, CDKN1B, GPR101 and the SDHx genes, while somatic driver mutations are well described in GNAS in somatotrophinomas and in USP8 in corticotrophinomas. Craniopharyngiomas are not heritable tumours, but there is a clear genetic basis at the somatic level, with clonal CTNNB1 and BRAF variants present in approximately 95% of adamantinomatous and papillary craniopharyngiomas, respectively. This review explores mechanistic developments in these established genes, new genes in the pituitary adenoma setting (e.g. MAX, CABLES1, CDH23, PAM or CHEK2), and emerging uses of CTNNB1/BRAF testing in the craniopharyngioma setting. It concludes with a discussion of the bench-to-bedside translations of these scientific discoveries as they pertain to clinicians seeing patients with these sellar tumours. In current clinical practice, the most readily applicable and directly impactful translations of recent pituitary genetic research are the opportunities for germline DNA testing for familial pituitary tumour syndromes and tumour DNA testing of craniopharyngiomas to confirm diagnosis (adamantinomatous/papillary craniopharyngioma) and guide treatment (in papillary craniopharyngioma).</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sexual dimorphism in thyroid cancer: evidence from preclinical studies.","authors":"Francesca Coperchini, Alessia Greco, Paolo Caccavale, Isabella Chiardi, Laura Croce, Marsida Teliti, Flavia Magri, Mario Rotondi","doi":"10.1530/ERC-24-0348","DOIUrl":"10.1530/ERC-24-0348","url":null,"abstract":"<p><p>Thyroid cancer (TC) exhibits strong sexual dimorphism, with higher incidence rates observed in females and more aggressive behavior in males. This disparity arises from complex interactions among genetic, hormonal and environmental factors. Data from preclinical studies evidenced a crucial role of sex hormones in driving TC prevalence and/or progression in males and females. In particular, estrogens would play a pro-tumorigenic role by directly activating estrogen receptor pathways and indirectly influencing tumorigenesis through mechanisms such as oxidative stress modulation, stimulation of thyroid stem cell proliferation, and alterations in the tumor microenvironment. Instead, androgens and androgen receptor (AR) signaling would exhibit dual roles in TC. AR downregulation in thyroid tissues is associated with increased tumor progression, whereas AR overexpression has demonstrated protective effects. These include inhibition of epithelial-to-mesenchymal transition, suppression of cell proliferation, downregulation of PD-L1 expression, and suppression of oncogenic microRNAs such as miR-146b. Conversely, androgens can promote tumor aggressiveness and metastasis in certain contexts, such as through VEGFC/VEGFR-3 signaling when a specific androgen-regulated gene is overexpressed. This review is aimed at summarizing the recent evidence coming from the literature data regarding both in vitro and in vivo studies on animal models investigating the multifaceted roles of sex hormones in TC, highlighting the critical need for new prospective longitudinal studies, also in view of gender-affirming hormones therapy. Such research will enhance our understanding of hormonal influences across diverse populations and further explain the relationship between sexual dimorphism and TC pathogenesis.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The genetic changes in 11p15.5-related pheochromocytomas and paragangliomas.","authors":"Pavla Jenčová, Tatiana Vosecká, Lucie Štolová, Marie Rychlá, Dagmar Voříšková, Tomáš Zelinka, Zdeněk Musil, Anasuya Guha, Jaroslava Dušková, Petr Brož, Ales Vicha","doi":"10.1530/ERC-24-0330","DOIUrl":"10.1530/ERC-24-0330","url":null,"abstract":"<p><p>Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors. The development of these tumors is associated with more than 20 genes. The aforementioned genes are subdivided into three clusters. The pseudohypoxic, kinase-signaling and Wnt clusters. The pseudohypoxic cluster is the only one that has been demonstrated to be associated with DNA methylation changes, including alterations in the 11p15.5 region. The objective of this study was to identify alterations in the 11p15.5 region, ascertain their prevalence in PPGLs, and subsequently compare them with the genomic and somatic mutations that cluster PPGLs. One hundred and fifty tumor samples were subjected to analysis. A total of 90 cases (60%) exhibited no alterations in the 11p15.5 region. The most prevalent alterations were maternal allele loss, observed in 45 cases (30%), pUPD (paternal uniparental disomy) in five cases (3.33%), and paternal allele gain in four cases (2.67%). The data presented here suggest that two mechanisms may be involved in the formation of PPGLs. These are reduced expression of CDKN1C (maternal allele deletion) and overexpression of IGF2 (pUPD, paternal allele gain). A statistically significant difference was observed in the frequency of alterations in the 11p15.5 region when comparing cluster 1 and cluster 2 (P-value <0.0001). This study is the first to describe pUPD and paternal allele gain as somatic alterations in PPGLs. In addition, our findings indicate that alterations in the 11p15.5 region are not exclusive to cluster 1. Consequently, the alterations in the 11p15.5 region cannot be regarded as a marker for cluster 1.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}