&lt;p&gt;A novel PDCD10 gene mutation in cerebral cavernous malformations: a case report and review of the literature&lt;/p&gt;

Yu, Weiwei; Jin, Haiqiang; You, Qian; Nan, Ding; Huang, Yining

doi:10.2147/jpr.s190317

Cited by 5 publications

(2 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Members of the PDCD gene family show extensive genetic similarities and are broadly expressed. PDCD genes have been linked to cell death [ 2 , 3 ], developmental problems, immunological illnesses, cancer, and other human diseases. PDCD10, which was first found in human premyeloid cells, is the gene activated in apoptotic cell death [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Pan-Cancer Analysis on the Oncogenic Role of Programmed Cell Death 10

Sun

Teng

et al. 2022

Journal of Oncology

View full text Add to dashboard Cite

Purpose. Programmed cell death factor 10 (PDCD10) is associated with intercellular junction, cytoskeleton organization, cell proliferation, apoptosis, exocytosis, and angiogenesis. However, the role of PDCD10 in human cancer is unclear. This study aims to explore the role of PDCD10 in various tumors and its possible mechanism through bioinformatics analysis. Methods. We verified the expression of the PDCD10 gene based on data from the ONCOMINE, TIMER2.0, and TISDB databases. The correlation of PDCD10 with prognosis of patients with different tumors was analyzed using data from the GEPIA2 database. Proteins bound to PDCD10 were analyzed from the STRING database. PDCD10, PDCD10-binding proteins, and associated candidate genes were analyzed in DAVID for functional and pathway analyses. We also evaluated the immunological, clinical, and genetic aspects of distinct cancers by using TIMER2.0 and the connection between PDCD10 expression and tumor immune subtypes by using TISDB. Single-cell sequencing data from the CancerSEA database were used to characterize cancer cell functional states and generate heat maps. Results. PDCD10 overexpression is linked to certain molecular subtypes of human cancer. Low PDCD10 expression in patients with bladder urothelial carcinoma (BLCA), lung adenocarcinoma (LUAD), liver hepatocellular carcinoma (LIHC), adrenocortical carcinoma (ACC), head and neck squamous cell carcinoma (HNSC), kidney chromophobe carcinoma (KICH), brain lower grade glioma (LGG), pancreatic adenocarcinoma (PAAD), uterine corpus endometrial carcinoma (UCEC), oral squamous cell carcinoma (OSCC), and esophageal adenocarcinoma (ESAD) was correlated with favorable OS, whereas high PDCD10 expression in patients with LUSC, KIRC, READ, SKCM, and THYM was correlated with good prognosis. STRING network prediction results showed that 20 proteins, namely, paxillin (PXN), CCM2 scaffold protein (CCM2), TRAF3 interacting protein 3 (TRAF3IP3), FGFR1 oncogene partner 2 (FGFR1OP2), chromosome 4 open reading frame 19 (C4orf19), suppressor of IKBKE 1 (SIKE1), serine/threonine kinase 25 (STK25), striatin (STRN), protein phosphatase 2 catalytic subunit alpha (PPP2CA), mammalian sterile-20-like kinase 4 (MST4), MOB family member 4 (MOB4), protein phosphatase 2 scaffold subunit Abeta (PPP2R1B), sarcolemma-associated protein (SLMAP), serine/threonine kinase 24 (STK24), striatin 4 (STRN4), STRN3, protein phosphatase 2 scaffold subunit A alpha (PPP2R1A), striatin interacting protein 1 (STRIP1), CTTNBP2 N-terminal like (CTTNBP2NL), and cortactin binding protein 2 (CTTNBP2), can bind to PDCD10. Gene enrichment analysis suggested that PDCD10 is involved in the occurrence of different tumors through the Hippo signalling pathway, RNA transport, mRNA monitoring pathway, endocytosis, and T cell receptor signalling pathway. An inverse relationship was found between PDCD10 expression and cancer-associated fibroblasts in LUSC and TGCT, and PDCD10 expression was strongly connected with immunological subtypes, such as C1 (wound healing), C2 (interferon-gamma dominant), C3 (inflammation), C4 (lymphocyte depletion), C5 (immune silenced), and C6 (TGF-beta dominant). Finally, analysis of single-cell sequencing data revealed that PDCD10 expression is linked to epigenetic reprogramming, DNA repair, cell cycle progression, cell differentiation, inflammation, cell proliferation, cell differentiation, cell invasion, and angiogenesis. Conclusion. The results of our investigation demonstrate that PDCD10 has an oncogenic function in many cancer types. This study provides a reference for future research on antitumor therapeutic targets.

show abstract

Section: Introductionmentioning

confidence: 99%

Pan-Cancer Analysis on the Oncogenic Role of Programmed Cell Death 10

Sun

Teng

et al. 2022

Journal of Oncology

View full text Add to dashboard Cite

show abstract

“…A typical image can be seen on T2-weighted MRI of the brain, which is characterized by a mulberry- or popcorn-like appearance in the center, surrounded by a dark rim. 4 CCM is caused genetically by loss-of-function mutations in one of the following three genes: KRIT1 (Krev1 Interaction Trapped 1)/ CCM1, MGC4607 (malcavermin)/ CCM2 , and PDCD10 (Programmed Cell Death 10)/ CCM3 . To date, more than 100, 30, and 20 distinct mutations have been identified in CCM1, CCM2 , and CCM3 , respectively.…”

Section: Introductionmentioning

confidence: 99%

A novel CCM3 mutation associated with cerebral cavernous malformation in a Chinese family

Jiang

Zhang

Yin

et al. 2020

Ther Adv Neurol Disord

View full text Add to dashboard Cite

Background: Cerebral cavernous malformation (CCM), especially the familial form, is a relatively rare congenital and occult vascular disease of the central nervous system. The familial form of CCM has been linked to three different genes: KRIT1/ CCM1, MGC4607/ CCM2, and PDCD10/ CCM3; however, the genetic basis of CCM is not well understood. The PDCD10/ CCM3 is the most recent gene to be identified that results in worse clinical symptoms. Early diagnosis and treatment is important for patient prognosis. Case report: The proband is a 38-year-old male who has been suffering from weakness in the limbs for 7 months. Investigation of his family history revealed that his mother also suffered from limbs paralysis and had been bedridden for a long time. His older brother suffered from headache for years, whereas his younger brother was asymptomatic. Brain computed tomography analysis of all family members showed multiple high-density shadows. Subsequently, magnetic resonance imaging analysis identified more prominent and similar multiple intracranial lesions in all family members. The lesions were hypo-intense, or showed mixed signs on T1-weighted imaging, and were significantly more intense on T2-weighted imaging. To understand the genetic basis of the disease in the family, DNA sequencing analysis was performed. A novel deletion mutation in the PDCD10/ CCM3 gene was identified in the proband and his relatives. The deletion resulted in a frameshift mutation and premature termination of translation of the protein, and potentially caused the disease in this family. Conclusions: Our study identified a novel PDCD10/ CCM3 heterozygous deletion (c.165delT) associated with CCM. This finding expands the CCM gene mutation profile, which will be beneficial for genetic counseling and clinical therapy.

show abstract

Comprehensive CCM3 Mutational Analysis in Two Patients with Syndromic Cerebral Cavernous Malformation

Galváo

Silva

Trefilio

et al. 2023

Transl. Stroke Res.

View full text Add to dashboard Cite

Cerebral Cavernous Malformation (CCM) is a vascular disease that affects the central nervous system, which familial form is due to autosomal dominant mutations in the genes KRIT1/CCM1, MGC4607/CCM2 and PDCD10/CCM3. Patients affected by the PDCD10 mutations usually have the onset of symptoms at an early age and a more aggressive phenotype. To contribute to knowledge about the disease, we performed clinical, functional, and neuroradiological analyses of the mutations in PDCD10/CCM3 in two patients comparing the ndings with ve patients with familial form from CCM1/KRIT1 or CCM2/MGC4607 mutations and six patients with sporadic form. In addition, we have evaluated the PDCD10/CCM3 gene expression by qPCR and developed a bioinformatic pipeline to assist in the possible clinical. The two CCM3 patients had an early onset of symptoms and a high lesion burden. Furthermore, the sequencing showed that P1 had a frameshift mutation (c.222delT;p.Asn75ThrfsTer14) and P2 a variant on the splicing region c.475-2A > G (p.A119Gfs*42). The mRNA expression was 4-fold lower in both patients with PDCD10/CCM3 mutation. In silico analysis, the prediction reveals that the frameshift mutation transcript lacks the C-terminal FAT-homology domain compared to the 212 aa-length wild-type PDCD10/CCM3 and preserves the N-terminal dimerization domain. We also demonstrated a related pathway that might explain the interplay between low-grade astrocytomas and PDCD10 CCM, a possible manifestation of the syndromic disease. The two mutations support the understanding of the protein-protein interaction between PDCD10 and several essential cellular proteins that might contribute to the mechanistic understanding of why some individuals with CCM3 have a syndromic phenotype.

show abstract

<p>A novel PDCD10 gene mutation in cerebral cavernous malformations: a case report and review of the literature</p>

Cited by 5 publications

References 48 publications

Pan-Cancer Analysis on the Oncogenic Role of Programmed Cell Death 10

Pan-Cancer Analysis on the Oncogenic Role of Programmed Cell Death 10

A novel CCM3 mutation associated with cerebral cavernous malformation in a Chinese family

Comprehensive CCM3 Mutational Analysis in Two Patients with Syndromic Cerebral Cavernous Malformation

Contact Info

Product

Resources

About