Objectives: Molecular characterization of sporadic pancreatic neuroendocrine tumors (PanNETs) demonstrates frequent alterations in MEN1. As the role of menin immunohistochemistry as a potential biomarker is being developed, knowledge of whether the pattern of menin expression is the same in primary tumors and distant metastases may help in patient care. Therefore, we compared patterns of menin expression in matched primary tumors and metastases.
Methods: We evaluated loss of menin nuclear expression by immunohistochemistry in 44 matched samples of primary and metastatic PanNETs and concordance in staining pattern between primary and metastatic tumors.
Results: Menin nuclear expression was lost in 18 (41%) of 44 primary tumors and 17 (39%) of 44 metastases. Concordant loss of menin expression was observed in 41 cases (93%); discordance was observed in 3 cases (7%; 95% confidence interval, 1.4%-18.7%), including 2 with loss in the primary tumor but not the metastasis.
Conclusions: The concordance of menin staining between primary tumor and metastasis in most cases suggests that menin loss is an early event in PanNET tumorigenesis. The discordant expression observed in a small subset may be a source of menin-directed therapy failure; thus, repeat assessment of metastases may be helpful for treatment selection.
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http://dx.doi.org/10.1097/MPA.0000000000001274 | DOI Listing |
Haematologica
December 2024
Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen.
Acute myeloid leukemia (AML) remains challenging to treat, which in part relates to genetic heterogeneity of the disease, to the protective tumor microenvironment driving resistance to therapy, and also to immune evasion characteristics of leukemic cells. Targeting epigenetic programs in AML provides an attractive opportunity to impair long-term proliferation and induce differentiation. The novel inhibitor JNJ- 75276617 (bleximenib) targets the menin-KMT2A interaction and provides preclinical efficacy in AML (Kwon et al1).
View Article and Find Full Text PDFEndocr Oncol
January 2024
Department of Molecular Medicine and Pathology, School of Medical Sciences, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Although the gene has a long-standing association with cancer, its mechanisms of action remain incompletely understood, acting both as a tumour suppressor in neuroendocrine tumours and as an oncogene in leukaemia. The best-characterised isoform of the encoded protein, MENIN, is the 610-amino acid MENIN isoform 2. We hypothesise that some of the complexity of biology can be attributed to a currently unappreciated contribution of different MENIN isoforms.
View Article and Find Full Text PDFFam Cancer
November 2024
Department of Pathology, UMC Utrecht, Utrecht University, Utrecht, The Netherlands.
Multiple endocrine neoplasia type 1 (MEN1) is a hereditary tumor syndrome characterized by endocrine tumors, typically from parathyroid, pancreatic, or anterior pituitary origin. In addition, benign cutaneous soft tissue tumors are prevalent in MEN1 patients. Although sarcomas have been reported in MEN1 patients it is unclear if these tumors should be considered as part of the MEN1 syndrome.
View Article and Find Full Text PDFPathologie (Heidelb)
November 2024
Department of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Nat Cell Biol
December 2024
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
RNA modification has emerged as an important epigenetic mechanism that controls abnormal metabolism and growth in acute myeloid leukaemia (AML). However, the roles of RNA N-acetylcytidine (ac4C) modification in AML remain elusive. Here, we report that ac4C and its catalytic enzyme NAT10 drive leukaemogenesis and sustain self-renewal of leukaemic stem cells/leukaemia-initiating cells through reprogramming serine metabolism.
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