Neurofibromatosis type 2 is an inherited disorder characterized by the development of benign and malignant tumors on the auditory nerves and central nervous system with symptoms including hearing loss, poor balance, skin lesions, and cataracts. Here, we report a novel protein-protein interaction between NF2 protein (merlin or schwannomin) and erythrocyte p55, also designated as MPP1. The p55 is a conserved scaffolding protein with postulated functions in cell shape, hair cell development, and neural patterning of the retina. The FERM domain of NF2 protein binds directly to p55, and surface plasmon resonance analysis indicates a specific interaction with a kD value of 3.7 nM. We developed a specific monoclonal antibody against human erythrocyte p55, and found that both p55 and NF2 proteins are colocalized in the non-myelin-forming Schwann cells. This finding suggests that the p55-NF2 protein interaction may play a functional role in the regulation of apico-basal polarity and tumor suppression pathways in non-erythroid cells.
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http://dx.doi.org/10.3181/0809-RM-275 | DOI Listing |
J Pathol
January 2025
Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
DICER1-associated sarcoma is an emerging entity, defined by either somatic or germline dicer 1, ribonuclease III (DICER1) mutations and sharing characteristic morphologic features irrespective of the site of origin. In addition to the DICER1 driver mutation, concurrent genomic alterations, including tumor protein 53 (TP53) inactivation and RAS pathway activation, are frequently detected. Tumors that morphologically resemble malignant peripheral nerve sheath tumor (MPNST) have rarely been reported among DICER1 sarcomas and often pose diagnostic challenges.
View Article and Find Full Text PDFSci Adv
January 2025
Institute of Pediatrics, Children's Hospital of Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, State Key Laboratory of Genetic Engineering, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
NF2-related schwannomatosis, previously known as neurofibromatosis type 2, is a genetic disorder characterized by nerve tumors due to gene mutations. Mice with deletion develop schwannomas slowly with low penetrance, hence inconvenient for preclinical studies. Here, we show that NF2, by recruiting E3 ubiquitin ligases β-TrCP1/2, promotes WWC1-3 ubiquitination and degradation.
View Article and Find Full Text PDFZhonghua Bing Li Xue Za Zhi
January 2025
Department of Pathology, School of Basic Medical Sciences, Peking University Third Hospital, Peking University Health Science Center, Beijing100191, China.
To understand the clinicopathological and molecular genetic characteristics of aggressive renal mucinous tubular and spindle cell carcinoma (MTSCC). The clinical features, histology, immunophenotype, molecular characteristics and prognosis of 4 cases of metastatic/recurrent renal MTSCC that were submitted to the Peking University Third Hospital (2 cases), Institute of Urology, Peking University (one case) and Zhejiang Provincial People's Hospital (one case) from 2015 to 2020 were retrospectively reviewed and analyzed. Among the four patients, two were male and two were female.
View Article and Find Full Text PDFSci Rep
December 2024
College of Life Sciences, Zhejiang University, Zhejiang, 310058, China.
Meningioma is the most prevalent primary intracranial tumor, with approximately half of patients harboring NF2 alteration. The rationale behind the presence of NF2 alteration in meningiomas and its absence in non-nerve system tumors remains elusive. Therefore, meningiomas and several non-nerve system tumor types were analyzed using KEGG analysis and CRISPR/Cas 9 technology to determine the role of NF2 in regulating tissue specificity.
View Article and Find Full Text PDFNeurooncol Adv
October 2024
Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Background: Ependymomas of the spinal cord are rare among children and adolescents, and the individual risk of disease progression is difficult to predict. This study aims to evaluate the prognostic impact of molecular typing on pediatric spinal cord ependymomas.
Methods: Eighty-three patients with spinal ependymomas ≤22 years registered in the HIT-MED database (German brain tumor registry for children, adolescents, and adults with medulloblastoma, ependymoma, pineoblastoma, and CNS-primitive neuroectodermal tumors) between 1992 and 2022 were included.
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