Endocrine-related cancer最新文献

Challenges and opportunities in systems biology education. 系统生物学教育的挑战与机遇。

Endocrine-related cancer Pub Date : 2025-06-19 Print Date: 2025-06-01 DOI: 10.1530/ERC-25-0024

Jeff Didier, Sophia Croce, Salma Bayoumi, Elena Valceschini, Hugues Escoffier, Evelyn Gonzalez, Ali Kishk, Apurva Badkas, Sébastien De Landtsheer, Thomas Sauter

引用次数: 0

Impact of multikinase inhibitors in reshaping the treatment of advanced gastroenteropancreatic neuroendocrine tumors. 多激酶抑制剂对晚期胃肠胰神经内分泌肿瘤治疗的影响。

Endocrine-related cancer Pub Date : 2025-06-18 Print Date: 2025-06-01 DOI: 10.1530/ERC-25-0052

Alexander R Siebenhüner, Julie Refardt, Guillaume P Nicolas, Reto Kaderli, Martin A Walter, Aurel Perren, Emanuel Christ

{"title":"Impact of multikinase inhibitors in reshaping the treatment of advanced gastroenteropancreatic neuroendocrine tumors.","authors":"Alexander R Siebenhüner, Julie Refardt, Guillaume P Nicolas, Reto Kaderli, Martin A Walter, Aurel Perren, Emanuel Christ","doi":"10.1530/ERC-25-0052","DOIUrl":"10.1530/ERC-25-0052","url":null,"abstract":"Neuroendocrine tumors (NETs) pose a considerable challenge due to their increasing incidence and frequently late-stage diagnosis. The arrival of multikinase inhibitors (MKIs) into clinical practice has brought notable progress in the management of advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs). This review aims at exploring the impact of MKIs in reshaping the treatment landscape for advanced GEP-NETs. Current approaches in managing advanced GEP-NETs are discussed, including somatostatin analogs, surgery, peptide receptor radionuclide therapy, and approved systemic treatments such as everolimus or sunitinib. The limitations and challenges faced in treating these tumors remain significant. Here, we review the clinical evidence supporting the use of everolimus as a targeted therapy, which has demonstrated improved progression-free survival (PFS), and the need for alternative therapies. Discussions focus on the clinical effectiveness and the emerging role of both established and novel MKIs in the treatment of GEP-NETs, including recent evidence from the CABINET trial and other emerging agents such as surufatinib, axitinib, pazopanib, and lenvatinib. We explore the clinical evidence that showcases sunitinib's and other MKIs' effectiveness in prolonging PFS compared to placebo in advanced GEP-NETs. Recently, MKIs have shown to have a significant impact for the treatment of advanced GEP-NETs. There remain several unmet needs that must be addressed, particularly regarding optimal treatment sequencing and the development of predictive biomarkers. Ongoing research and the use of current and emerging MKIs hold great potential to advance the treatment landscape for advanced GEP-NETs significantly.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12177888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113210","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}

引用次数: 0

Pituitary tumor-transforming gene 1 and endocrine cancers: an up-to-date review through history, current insights and future perspectives. 垂体肿瘤转化基因1和内分泌癌：通过历史，当前见解和未来观点的最新综述。

Endocrine-related cancer Pub Date : 2025-06-18 Print Date: 2025-06-01 DOI: 10.1530/ERC-24-0163

E Vergani, E Teveroni, F Mancini, F Di Nicuolo, S Raia, S Chiloiro, F Pierconti, A Bianchi, A M Isidori, A Pontecorvi, D Milardi

{"title":"Pituitary tumor-transforming gene 1 and endocrine cancers: an up-to-date review through history, current insights and future perspectives.","authors":"E Vergani, E Teveroni, F Mancini, F Di Nicuolo, S Raia, S Chiloiro, F Pierconti, A Bianchi, A M Isidori, A Pontecorvi, D Milardi","doi":"10.1530/ERC-24-0163","DOIUrl":"10.1530/ERC-24-0163","url":null,"abstract":"Pituitary tumor-transforming gene 1 (PTTG1), discovered in 1997 by Pei and Melmed, takes part in cellular replication, cell cycle control, DNA repair mechanisms, organogenesis, metabolism regulation, cellular transformation, and senescence. Its biological actions include protein-protein interactions, modulation of gene transcription, and other than intracellular and autocrine mechanisms, even paracrine activities. For the reasons mentioned above, PTTG1 stands out as a multifaceted regulator of cancer biology; it is involved in genomic and chromosomal instability, local invasiveness, neo-lymphangiogenesis, and metastatic spreading. In solid neoplasms, endocrine neoplasms, although deemed rare, have experienced a significant increase in diagnostic incidence in recent years. Endocrine cancers are still a major challenge in healthcare and research since several questions remain unanswered, even though researchers have made considerable efforts to uncover their causes. Twenty-seven years have passed since PTTG1's discovery, and several works have been published. However, only the tip of the iceberg has been unveiled. Herein, we review current knowledge of PTTG1's action in endocrine cancers, such as pituitary, thyroid, testicular, adrenal, pancreatic, and ovarian.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236219","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}

引用次数: 0

Challenges in circulating miRNA analysis in adrenocortical tumors. 肾上腺皮质肿瘤循环miRNA分析的挑战。

Endocrine-related cancer Pub Date : 2025-06-17 Print Date: 2025-06-01 DOI: 10.1530/ERC-25-0045

Bálint Vékony, Gábor Nyirő, Henriett Butz, Bálint Kende Szeredás, Viktória Tóth, Peter Ferdinandy, Attila Patócs, Peter Igaz

{"title":"Challenges in circulating miRNA analysis in adrenocortical tumors.","authors":"Bálint Vékony, Gábor Nyirő, Henriett Butz, Bálint Kende Szeredás, Viktória Tóth, Peter Ferdinandy, Attila Patócs, Peter Igaz","doi":"10.1530/ERC-25-0045","DOIUrl":"10.1530/ERC-25-0045","url":null,"abstract":"The differentiation of benign and malignant adrenocortical tumors is of major clinical relevance. Circulating microRNAs (miRNAs) hold promise as blood-borne biomarkers of adrenocortical cancer (ACC). There are, however, many difficulties with their use, including technical and biological standardization challenges. Our aim was to evaluate the interchangeability of quantitative polymerase chain reaction (qPCR) and digital PCR (dPCR) for measuring circulating miRNAs and to investigate whether K2- and K3-EDTA as anticoagulants influence the measurements. Blood samples were drawn simultaneously from 20 participants into K2- and K3-EDTA tubes. Three miRNAs shown to be associated with ACC (miR-483-5p, miR-210-3p, miR-21-5p), together with two controls (miR-16-5p, cel-miR-39-3p), were analyzed using RT-qPCR and dPCR. qPCR and dPCR results showed different correlations in K2- and K3-EDTA samples, with K2 performing better regarding ΔCt values. Moreover, proportional biases related to low or high miRNA expressions between the two methods were observed. In qPCR measurements, K3-EDTA samples showed larger standard deviations, particularly for cel-miR-39. While raw Ct values differed between K2- and K3-EDTA only for miR-483-5p, ΔCt values showed statistically significant differences across all miRNAs except for miR-483-5p. dPCR results were not affected by the choice of anticoagulant. In conclusion, this is the first study demonstrating that dPCR and qPCR results are not easily interchangeable for circulating miRNA, particularly for abundant or rare miRNAs, making cross-validation studies challenging. K2- and K3-EDTA could potentially influence qPCR outcomes, underscoring the need for standardized protocols. A consensus-based methodology could improve reproducibility, enhancing miRNA-based biomarker utility in adrenocortical tumor diagnostics.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236218","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}

引用次数: 0

FAM64A contributes to ovarian cancer proliferation and metastasis by suppressing TWIST1 ubiquitination and degradation. FAM64A通过抑制TWIST1泛素化降解参与卵巢癌的增殖和转移。

Endocrine-related cancer Pub Date : 2025-06-16 Print Date: 2025-06-01 DOI: 10.1530/ERC-24-0048

Juan Zhao, Ting Yang, Sijuan Tian, Meili Pei, Minyi Zhao, Li Wang, Xiaofeng Yang

{"title":"FAM64A contributes to ovarian cancer proliferation and metastasis by suppressing TWIST1 ubiquitination and degradation.","authors":"Juan Zhao, Ting Yang, Sijuan Tian, Meili Pei, Minyi Zhao, Li Wang, Xiaofeng Yang","doi":"10.1530/ERC-24-0048","DOIUrl":"10.1530/ERC-24-0048","url":null,"abstract":"Ovarian cancer is among the most common cancers among gynecological malignancies. FAM64A is associated with various cancer progressions, but its function and mechanism in ovarian cancer remain unclear. We analyzed and examined the expression of FAM64A in ovarian cancer cells and tissues. Proliferation, migration and invasion were assessed by knocking down and overexpressing FAM64A in A2780 and SKOV3 cells, respectively. Bioinformatics combined with molecular experiments validated the molecular mechanism of FAM64A. A xenograft tumor model and lung metastasis model were created to explore the impact of FAM64A on tumor growth and metastasis in nude mice. To evaluate the relative signaling molecule expression, immunohistochemistry (IHC) and western blot assays were conducted. FAM64A was upregulated in ovarian cancer tissues and cells and was demonstrated to promote the proliferation, migration and invasion of A2780 and SKOV3 cells in vitro. Bioinformatics and western blot assays indicated that FAM64A could regulate the EMT-related transcription factor TWIST1 by suppressing TWIST1 ubiquitination and degradation via the E3 ubiquitin ligase STUB1. Moreover, the knockdown of FAM64A inhibited tumor growth in xenograft tumor mice and lung metastasis in vivo. FAM64A exerts its oncogenic function by regulating TWIST1 ubiquitination and degradation, indicating that FAM64A may provide a promising therapeutic target for the treatment of ovarian cancer.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153096","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}

引用次数: 0

Endocrine-related cancer Pub Date : 2025-06-16 Print Date: 2025-06-01 DOI: 10.1530/ERC-25-0025

Yael Kusne, Mrinal M Patnaik, Thorvardur R Halfdanarson, Mohamad Bassam Sonbol

{"title":"Therapy-related myeloid neoplasms in 177Lu-DOTATATE treated neuroendocrine tumor patients: how great is the risk?","authors":"Yael Kusne, Mrinal M Patnaik, Thorvardur R Halfdanarson, Mohamad Bassam Sonbol","doi":"10.1530/ERC-25-0025","DOIUrl":"10.1530/ERC-25-0025","url":null,"abstract":"Peptide receptor radionuclide therapy (PRRT) with lutetium-177-Dotatate (177Lu-DOTATATE) has transformed neuroendocrine tumor (NET) treatment, improving progression-free survival, symptom control, and quality of life. However, long-term hematologic toxicities, including therapy-related myeloid neoplasms (tMN), are increasingly recognized. These rare but severe complications, such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), appear multifactorial, influenced by prior cytotoxic therapies, radiation exposure, clonal hematopoiesis, and germline predispositions. This review synthesizes data on PRRT-related hematologic toxicities, including findings from pivotal studies and real-world evidence. We explore risk factors, underlying mechanisms, and the potential role of biomarkers, such as clonal hematopoiesis and germline mutations, in predicting toxicity. Emerging approaches, including alpha particle radioligand therapy and advanced dosimetry, are explored as strategies to optimize patient selection and minimize adverse outcomes. To maximize the benefits of PRRT while safeguarding patient safety, future efforts should focus on integrating predictive biomarkers, refining treatment sequencing, and developing personalized risk-stratified approaches to therapy.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188664","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}

引用次数: 0

Peptide receptor radionuclide therapy in malignant insulinoma. 肽受体放射性核素治疗恶性胰岛素瘤。

Endocrine-related cancer Pub Date : 2025-06-14 Print Date: 2025-06-01 DOI: 10.1530/ERC-25-0018

David A Pattison, Grace Kong, Timothy Akhurst, Matthew Burge, Cherie Chiang, Michael S Hofman, Te-Jui Hung, Amanda Love, Michael Michael, Satomi Okano, Aravind S Ravi Kumar, Nirupa Sachithanandan, David Wyld, Rodney J Hicks

{"title":"Peptide receptor radionuclide therapy in malignant insulinoma.","authors":"David A Pattison, Grace Kong, Timothy Akhurst, Matthew Burge, Cherie Chiang, Michael S Hofman, Te-Jui Hung, Amanda Love, Michael Michael, Satomi Okano, Aravind S Ravi Kumar, Nirupa Sachithanandan, David Wyld, Rodney J Hicks","doi":"10.1530/ERC-25-0018","DOIUrl":"10.1530/ERC-25-0018","url":null,"abstract":"The management of malignant insulinoma (MI) presents dual management challenges of hypoglycaemia and tumour control. This study aims to analyse long-term outcomes of PRRT for the treatment of MI. We retrospectively reviewed consecutive patients with MI treated with [177Lu]Lu-DOTATATE (LuTATE) at two Australian NET centres between 2004 and 2022. Follow-up for hypoglycaemia, molecular imaging, radiologic and biochemical responses, treatment-related side-effects, progression-free and overall survival were assessed. Of 15 patients (seven female; median age 60, range 26-82) treated for intractable hypoglycaemia, WHO grade (G) was known in 12 patients (three G1, six G2 and three G3). PRRT was administered in a median of seven cycles (range 1-15), with a median cumulative activity of 42 GBq (range 4-117 GBq) and radiosensitizing chemotherapy in 9/15 (60%) patients. Resolution of hypoglycaemia was observed in 14/15 (93%) patients after a median of 2.5 months (range 0.2-23.5), but recurred in 7/14 cases after a median of 17.7 months (range 7.6-48.3). Patients with recurrent hypoglycaemia had a longer time to hypoglycaemia resolution (median 3.0 vs 0.5 months), were more likely G3 (57 vs 0%) and experienced higher mortality (86 vs 29%). In all seven cases, PRRT re-treatment was successful. The mean duration of hypoglycaemia remission was 23.8 months (range 9.2-101). The median progression-free and overall survival was 17.9 months (95% CI, 8.5-43.2) and 50.1 months (95% CI, 23.0-ND), respectively. Side-effects included G3/4 myelosuppression in 4/15 patients and hypoglycaemia flare (hospitalisation >48 h) in 7/15 patients. PRRT provides durable hypoglycaemic and oncologic disease control of MI with manageable toxicity including hypoglycaemia flare requiring multidisciplinary care.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153038","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}

引用次数: 0

Transcriptome sequencing reveals distinct atypical parathyroid tumor subtypes. 转录组测序显示不同的非典型甲状旁腺肿瘤亚型。

Endocrine-related cancer Pub Date : 2025-06-14 Print Date: 2025-06-01 DOI: 10.1530/ERC-25-0057

Hye-Sun Park, Milim Kim, Se-Young Jo, Gi Jeong Kim, Jong Ju Jeong, Namki Hong, Sangwoo Kim, Yumie Rhee

{"title":"Transcriptome sequencing reveals distinct atypical parathyroid tumor subtypes.","authors":"Hye-Sun Park, Milim Kim, Se-Young Jo, Gi Jeong Kim, Jong Ju Jeong, Namki Hong, Sangwoo Kim, Yumie Rhee","doi":"10.1530/ERC-25-0057","DOIUrl":"10.1530/ERC-25-0057","url":null,"abstract":"Atypical parathyroid tumors (APTs) are a rare subtype of parathyroid neoplasms characterized by diagnostic challenges and an uncertain prognosis. This study aimed to validate the subtypes of APTs using transcriptome sequencing. We applied a clustering model developed for our previous study in which we had successfully distinguished parathyroid cancer from adenomas using gene expression patterns. Sixteen patients with APT who had undergone parathyroidectomy were enrolled, and we analyzed their baseline data, pathologic reports and follow-up records and performed transcriptome sequencing of their APT samples. We then used our clustering model to classify tumors as either cancer- or adenoma-type APTs and compared these results with clinical findings. The median age of patients was 48.9 years, with median calcium and parathyroid hormone (PTH) levels of 11.4 mg/dL and 420.0 pg/mL, respectively. Pathologic and immunohistochemical results did not reveal any remarkable differences between adenoma-type and cancer-type APTs. However, clustering analysis classified four of the 16 APTs as being cancer-type and 12 as being adenoma-type tumors. Cancer-type patients had a median age of 30.0 years, with median calcium and PTH levels of 12.6 mg/dL and 800.8 pg/mL, respectively, clinically resembling parathyroid cancer. One patient exhibited a somatic CDC73 two-hit mutation and positive WT1 staining, suggesting a high malignant potential. Clustering analysis through transcriptome sequencing shows promise for risk stratification of patients with APTs. For those classified as having cancer-type tumors, close monitoring and long-term follow-up may be warranted.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144164077","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}

引用次数: 0

Comparative efficacy of systemic therapies in malignant insulinoma. 恶性胰岛素瘤全身治疗的比较疗效。

Endocrine-related cancer Pub Date : 2025-06-10 Print Date: 2025-06-01 DOI: 10.1530/ERC-25-0091

Regina Koch, Patrick Walsh McGarrah, Adrian Vella, Pankaj Shah, Timothy J Hobday, Mohamed Bassam Sonbol, Jason Starr, Rachel Eiring, Travis J McKenzie, Alaa Sada, Patrick Starlinger, Hallbera Gudmundsdottir, Thorvadur R Halfdanarson

{"title":"Comparative efficacy of systemic therapies in malignant insulinoma.","authors":"Regina Koch, Patrick Walsh McGarrah, Adrian Vella, Pankaj Shah, Timothy J Hobday, Mohamed Bassam Sonbol, Jason Starr, Rachel Eiring, Travis J McKenzie, Alaa Sada, Patrick Starlinger, Hallbera Gudmundsdottir, Thorvadur R Halfdanarson","doi":"10.1530/ERC-25-0091","DOIUrl":"10.1530/ERC-25-0091","url":null,"abstract":"Malignant insulinomas are rare pancreatic neuroendocrine tumors characterized by excessive insulin secretion and a high propensity for metastasis, leading to challenging management. This study retrospectively analyzed 57 patients treated for malignant insulinoma at Mayo Clinic sites between 1992 and 2024, focusing on the efficacy of systemic therapies in improving hypoglycemic control and survival outcomes. The most commonly used therapies included somatostatin analogs (SSA), everolimus, capecitabine-temozolomide (CAPTEM), and peptide receptor radionuclide therapy (PRRT). PRRT demonstrated the highest efficacy in controlling hypoglycemia (93%), followed by CAPTEM (68%) and everolimus (62%). SSA, chemotherapy, and streptozocin were less effective, with hypoglycemic improvement seen in 37.5, 33.3, and 28.6% of patients, respectively. Overall survival (OS) was longest with SSA at 84.67 months, followed by CAPTEM at 81.67 months and everolimus at 74.07 months. PRRT demonstrated a median OS of 49.73 months. In contrast, chemotherapy and streptozocin-based therapies had significantly shorter OS times of 15.23 and 8.35 months, respectively. These findings highlight significant variability in systemic therapy efficacy for malignant insulinoma, with PRRT emerging as a promising treatment for refractory hypoglycemia and long survival. Cox regression analysis identified primary tumor resection and a history of benign insulinoma as associated with longer OS. Optimal sequencing of therapies remains unclear, and individualized treatment plans based on hypoglycemic burden and tumor characteristics are critical for improving survival and quality of life in these patients.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176207","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}

引用次数: 0

Familial Mahvash disease with metastatic pancreatic NET and MEN1 mutations. 家族性Mahvash病伴转移性胰腺NET和MEN1突变。

Endocrine-related cancer Pub Date : 2025-06-09 Print Date: 2025-06-01 DOI: 10.1530/ERC-25-0087

Jelka Kuiper, Wouter W de Herder, Yassine Ben Brahim, Marie-Louise F van Velthuysen, Lodewijk A A Brosens, Richard A Feelders, Janneke G Langendonk, Ronald van Marion, Esther Korpershoek, Günter Klöppel, Anja Wagner, Johannes Hofland

{"title":"Familial Mahvash disease with metastatic pancreatic NET and MEN1 mutations.","authors":"Jelka Kuiper, Wouter W de Herder, Yassine Ben Brahim, Marie-Louise F van Velthuysen, Lodewijk A A Brosens, Richard A Feelders, Janneke G Langendonk, Ronald van Marion, Esther Korpershoek, Günter Klöppel, Anja Wagner, Johannes Hofland","doi":"10.1530/ERC-25-0087","DOIUrl":"10.1530/ERC-25-0087","url":null,"abstract":"Homozygous pathogenic glucagon receptor gene (GCGR) mutations cause a syndrome with pancreatic glucagon cell hyperplasia and neoplasia (GCHN) and hyperglucagonaemia without a glucagonoma syndrome named Mahvash disease. The disease follows an autosomal recessive course and is an exceptionally rare hereditary pancreatic neuroendocrine tumour (panNET) syndrome, with only seven cases documented in the literature. The study aims to elucidate the genotype-phenotype correlation in Mahvash disease and panNET development. Clinical features, molecular profile, pancreatic pathology, and follow-up were studied in detail in six of the 11 family members. The patients' medical records were reviewed up until November 2024. Eight family members were positive for the likely pathogenic GCGR c.455C>T (p.Ser152Phe) germline variant. Three of the family members were homozygous for the GCGR germline variant. Two homozygous patients showed GCHN in pancreatic resection samples, with one exhibiting lymphogenic and hepatic metastases. Three patients had a glucagon-positive tumour with distinct somatic mutations in the MEN1 gene. One family member, heterozygous for the GCGR variant, presented with three small panNET, with the one biopsied lesion showing glucagon immunoreactivity. We report the first study of a single family with multiple members presenting with GCNH caused by a novel germline GCGR variant. We are also presenting the first patient with liver metastases in GCHN and another patient with multiple small panNET heterozygous for the novel GCGR gene variant. Our observations highlight the malignant potential for GCHN and suggest that somatic MEN1 mutations may play a role in the development of glucagon-positive panNET from glucagon cell hyperplasia.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153097","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}

引用次数: 0