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The clinical data of a child with MORC2 gene mutation related neurodevelopmental disorder treated in Fujian Medical University Union Hospital in July 2020 were analyzed retrospectively.The male (7-year-old)patient was global retardation from infant, with special face, short stature, small head circumference, decreased muscle strength and positive pyramidal tract sign of lower limbs.Brain magnetic resonance imaging was similar to the changes of Leigh syndrome.Genetic testing found de novo mutation in MORC2 gene chr22: 31345763, c.292G>A(p.Gly98Arg). And literature review found that there was only one related report. MORC2 gene mutation related neurodevelopmental disorder is a newly discovered syndrome, and c. 79G>A(p.Glu27Lys) is the most common mutation.This case enriched the clinical phenotype and genotype of neurodevelopmental disorder related to MORC2 gene.
ABSTRACT
Objective To investigate the expression of microrchidia 2(MORC2) in glioblastoma patients and to evaluate its prognostic value of MORC2 expression combined with IDH1 mutation status for chemoradiotherapy efficacy and new molecular subtype.Methods The expression level of MORC2 in 45 glioblastoma tissues was measured by immunohistochemical staining and its correlation with clinicopathological characteristics and clinical prognosis after chemoradiotherapy was analyzed.Further more,the prognostic values of the expression of MORC2 combined with the status of IDH1 were assessed in a glioblastoma CGGA mRNA dataset.Results High expression of MORC2 was observed in 76％ of glioblastoma patients,which was negatively correlated with overall survival (HR=2.928,95％CI:1.582-5.418,P=0.002;recurrence-free survival (HR=2.204,95％CI:1.186-4.095,P=0.022).Moreover,according to the prognosis value of MORC2 expression and IDH1 mutation status,glioblastoma patients were divided into 3 molecular subtypes.Patients with the subtype of IDH1mt/MORC2low obtained the best clinical prognosis with a median survival of 22 months (95％CI:13.98-30.02),whereas those with the subtype of IDH1wt/MORC2high obtained the worst clinical prognosis with a median survival of 5.63 months (95％CI:3.92-7.34,HR=4.15,95％CI:3.92-7.34,P=0.002).Among IDH1wt glioblastoma patients,MORC2high patients had worse clinical prognosis compared with MORC2low counterparts,prompting that IDH1wt/ MORC2high glioblastoma tissues yielded higher capability of DNA injury repairing and resistance to chemoradiotherapy.Conclusions The high expression of MORC2 can be used as a potential indicator of poor prognosis of glioblastoma patients after chemoradiotherapy.IDH 1 mutation status combined with MORC2 expression can establish a novel molecular subtyping,which provide evidence for stratified therapy for glioblastoma patients.
ABSTRACT
Background and purpose: MORC2 (microrchidia family CW-type zinc finger 2, MORC2) is a newly identified chromatin remodeling protein that plays key roles in DNA-based biological processes including gene transcription and DNA damage repair. However, its functional role in breast cancer development and progression re-mains unknown. ALDH1A3 (aldehyde dehydrogenase 1 family member A3), a member of the aldehyde dehydrogenases (ALDH) superfamily, is a putative breast cancer stem cell marker, but its regulatory mechanism in breast cancer is poor-ly characterized. This study aimed to investigate the effects of knockdown of endogenous MORC2 on the expression levels of ALDH1A3 and the breast cancer stem-like phenotype in MCF-7 cells. Methods: Human breast cancer MCF-7 cells were infected with negative control short hairpin RNAs (shNC) and specific shRNAs targeting human MORC2 (shMORC2), followed by selection with puromycin to generate stable MORC2 gene knockdown cell lines. Western blot and real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR) were used to examine the protein and mRNA levels of ALDH1A3 in MCF-7 cells stably expressing shNC and shMORC2. Microsphere formation and fluo-rescence-activated cell sorting (FACS) assays were used to analyze the effects of knockdown of MORC2 on the breast cancer stem-like phenotype. Results: Western blot and RTFQ-PCR analyses revealed that the protein and mRNA levels of ALDH1A3 were significantly down-regulated in shMORC2 expressing cells as compared with shNC -transfected control cells. Moreover, mammosphere formation assay showed that knockdown of endogenous MORC2 in MCF-7 cells significantly reduced the ability of cells to form microspheres. Consistently, FACS assays demonstrated that shMORC2-transfected cells had a lower proportion of ALDH-positive stem cells as compared with shNC expressing cells. In contrast, knockdown of MORC2 did not significantly affect the CD44+CD24- stem cell population. Conclusion:MORC2 promotes a breast cancer stem-like phenotype through, at least in part, regulating ALDH1A3 expression.