Analysis of sebaceous gland carcinoma associated genes using network analysis to identify potentially actionable genes

Eyelid sebaceous gland carcinoma (SGC) is a rare but life-threatening condi-tion. However, there is limited computational research associated with un-derlying protein interactions specific to eyelid sebaceous gland carcinoma. The aim of our study is to identify and analyse the genes associated with eyelid sebaceous gland carcinoma using text mining and to develop a protein-protein interaction network to predict significant biological pathways using bioinformatics tool. Genes associated with eyelid sebaceous gland carcinoma were retrieved from the PubMed database using text mining with key terms ‘eyelid’, ‘sebaceous gland carcinoma’ and excluding the genes for ‘Muir-Torre Syndrome’. The interaction partners were identified using STRING. Cytoscape was used for visualization and analysis of the PPI network. Molec-ular complexes in the network were predicted using MCODE plug-in and ana-lyzed for gene ontology terms using DAVID. PubMed retrieval process identi-fied 79 genes related to eyelid sebaceous gland carcinoma. The PPI network associated with eyelid sebaceous gland carcinoma produced 79 nodes, 1768 edges. Network analysis using Cytoscape identified nine key genes and two molecular complexes to be enriched in the protein-protein interaction net-work. GO enrichment analysis identified biological processes cell fate com-mitment, Wnt signalling pathway, retinoic acid signalling and response to cytokines to be enriched in our network. Genes identified in the study might play a pivotal role in understanding the underlying molecular pathways in-volved in the development and progression of eyelid sebaceous gland carci-noma. Furthermore, it may aid in the identification of candidate biomarkers and therapeutic targets in the treatment of eyelid sebaceous gland carcino-ma.

Ten-year epidemiological study of ocular and orbital tumors in Chiba University Hospital

Background The purpose of this study is to determine the epidemiology of tumors of the ocular adnexa and orbit in Japan. Methods We conducted a retrospective study on the histopathological reports in the medical records of the Chiba University Hospital from April 2009 to March 2019. Three hundred and seventy two records were examined. In addition, we examined the annual changes in the major types of tumors including malignant lymphomas and IgG4-related diseases (IgG4-RDs). Results There were 270 conjunctival or eyelid tumors with 166 benign and 104 malignant. There were 102 orbital tumors with 55 benign, 47 malignant tumors, and 21 cases of IgG4-RDs. Ten cases of adenoma (2.7%), another benign tumor, was also diagnosed. The major malignant tumors were malignant lymphoma in 74 cases, sebaceous gland carcinoma (SGC) in 28 cases, basal cell carcinoma in 15 cases, and squamous cell carcinoma in 8 cases. The SGCs were the most common malignant eyelid tumor at 54%. Among the malignant lymphomas, extranodal marginal zone lymphomas of the mucosa-associated lymphoid tissue type, MALT lymphomas, was the most common at 51 cases and the second most common was the diffuse large B-cell lymphoma at 11 cases. The ratio of MALT lymphomas to that of all malignant lymphomas increased significantly with years. The serum IgG4 values were measured more often in the last 5 years (70%) than in the former 5 years (33%). Conclusions We conclude that malignant lymphoma is a major malignant tumor in Japan and pathological biopsies should be done proactively to prevent missing IgG4-positive MALT lymphomas.

Sebaceous gland carcinoma of ocular region in India: A brief literature review for disease management

Sebaceous gland carcinoma (SGC) is slow growing, but the most aggressive and lethal eyelid malignancy. Histologically, SGC can be classified based on cell types, cytoarchitecture, and growth patterns. A previously published article illustrates the molecular genetic framework stating the drivers of sebaceous carcinoma. Today, every effort has been made to treat and eradicate ocular disease, therefore, early diagnosis and appropriate management are required to use a multimodal approach that can reduce the mortality rate in patients with SGC. Treatment with the conventional technique has improved visual and systemic prognosis, however, therapeutic target to treat cancer is a much better option than other modalities. Thus, new insight into the natural and molecular-oriented treatment modalities may lead to the development of new effective strategies, along with the conventional method.

Clinicopathological analysis of 5146 eyelid tumours and tumour-like lesions in an eye centre in South China, 2000–2018: a retrospective cohort study

ObjectivesTo describe the clinicopathological characteristics of patients with eyelid tumours and tumour-like lesions in South China, investigate possible factors affecting tumour constitution.DesignRetrospective cohort study.SettingAll patients diagnosed with eyelid tumours were included from a high-volume tertiary eye care centre from South China which caring for over 2000 patients per day. All biopsied specimens were reviewed by two senior pathologists and were classified according to the fourth edition of the WHO Classification of Skin Tumours.ParticipantA total of 5146 cases of eyelid lesions were reviewed from 2000 to 2018, being classified by histogenesis and pathologic diagnosis, being compared with data from previous literature containing different races.Main outcome measuresAge-specific and gender-specific incidence constitutions, time trends, tumour location, distribution in different age groups and relationship with Sociodmographic Index (SDI) were calculated.ResultsBenign tumours accounted for 85.08% (4378) of all cases, among which, nevus was most common (33.07%). Eight of top 10 benign lesions had higher occurrence in upper eyelids. The R² value of linear regression in patient annual number of benign lesions were 0.946 (p<0.01) for male and 0.914 (p<0.01) for female. More than 33.60% (1471/4378) were made up by patients younger than 40 years. The number of patients undergoing removal of benign lesions decreased with age. Among the malignant lesions, basal cell carcinoma (BCC) was most prevalent (48.70%), followed by sebaceous gland carcinoma (34.24%) and majority (81.8%) occurred in patients above 60 years.ConclusionsOver the past 19 years, most eyelid tumours occurred at our centre were benign lesions. The number of patients presenting with benign lesions increased in both genders, especially among young females who were more likely to request surgeries. Among malignant lesions, BCC remains the most common type, appears a higher incidence in countries with higher SDI.

In cis TP53 and RAD51C pathogenic variants may predispose to sebaceous gland carcinomas

Pathogenic variants in TP53 have been classically thought to cause Li-Fraumeni syndrome (LFS), a cancer predisposition with high risks for various childhood- and adult-onset malignancies. However, increased genetic testing has lately revealed, that pathogenic variant carriers exhibit a broader range of phenotypes and that penetrance may be dependent both on variant type and modifiers. Using next generation sequencing and short tandem repeat analysis, we identified germline pathogenic variants in TP53 and RAD51C located in cis on chromosome 17 in a 43-year-old male, who has developed a rare sebaceous gland carcinoma (SGC) but so far no tumors of the LFS spectrum. This course mirrors a Trp53-Rad51c-double-mutant cis mouse-model, which similarly develops SGC, while the characteristic Trp53-associated tumor spectrum occurs with significantly lower frequency. Therefore, we propose that co-occurent pathogenic variants in RAD51C and TP53 may predispose to SGC, reminiscent of Muir-Torre syndrome. Further, this report supports the diversity of clinical presentations associated with germline TP53 alterations, and thus, the proposed expansion of LFS to heritable TP53-related cancer syndrome.