Last twenty-years activity of cardiovascular tissue banking in Barcelona.

The Barcelona Tissue Bank was established from the merge of two previous multi-tissue banks. Potential donors are screened by Donor Center staff and multi-tissue retrieval is performed by specialized own teams. Tissue processing and preservation is performed in clean room facilities by specialised personnel. After quality control of both donor and all tissues results, the heart valves and vascular segments are stored until medical request. The aim of this report is to present the cardiovascular tissue activity and retrospectively evaluate the outcomes of the changes performed in last 20 years. Cardiovascular tissue from 4088 donors was received, specifically 3115 hearts and 2095 vascular segments were processed and evaluated. A total of 48% of the aortic valves, 68% of the pulmonary valves and 75% of the vascular segments were suitable for transplant. The main reason for discarding tissue was macroscopic morphology followed by microbiological results, for both valves and arteries. Altogether, 4360 tissues were distributed for transplantation: 2032 (47%) vascular segments, 1545 (35%) pulmonary valves and 781 (18%) aortic valves. The most common indication for aortic valve surgery was the treatment of endocarditis, while for pulmonary valves, it was congenital malformation reconstruction. Vascular segments were mainly used for reconstruction after ischemia. During this period, a number of changes were made with the goal of enhancing tissue quality, safety and efficacy. These improvements were achieved through the use of a new antibiotic cocktail, increasing of donor age criteria and changing the microbiological control strategy.

The Landscape of US and Global Rare Tumor Research Programs: A Systematic Review.

Rare cancers and other rare nonmalignant tumors comprise 25% of all cancer diagnoses and account for 25% of all cancer deaths. They are difficult to study due to many factors, including infrequent occurrence, lack of a universal infrastructure for data and/or tissue collection, and a paucity of disease models to test potential treatments. For each individual rare cancer, the limited number of diagnosed cases makes it difficult to recruit sufficient patients for clinical studies, and rare cancer research studies are often siloed. As a result, progress has been slow for many of these cancers. While rare cancer research efforts have increased over time, the breadth of the research landscape is not known. A recent literature search revealed a sharp increase in rare tumor, and rare cancer publications began in the early 2000s. To identify rare cancer research efforts being conducted in the US and globally, we conducted an online search of rare tumor/rare cancer research programs and identified 76 programs. To gain a deeper understanding of these programs, we composed and conducted a survey to ask programs for details about their research efforts. Of the 42 programs contacted to complete the survey, 23 programs responded. Survey results show most programs are collecting clinical data, molecular data, and biospecimens, and many are conducting molecular analyses. This landscape analysis demonstrates that multiple rare cancer research efforts are ongoing, and the rare cancer community may benefit from collaboration among stakeholders to accelerate research and improve patient outcomes.

Sourcing and development of tissue for transplantation in reconstructive surgery: A narrative review.

The wealth of allogeneic and xenogeneic tissue products available to plastic and reconstructive surgeons has allowed for the development of novel surgical solutions to challenging clinical problems, often obviating the need to inflict donor site morbidity. Allogeneic tissue used for reconstructive surgery enters the tissue industry through whole body donation or reproductive tissue donation and has been regulated by the FDA as human cells, tissues, and cellular and tissue-based products (HCT/Ps) since 1997. Tissue banks offering allogeneic tissue can also undergo voluntary regulation by the American Association of Tissue Banks (AATB). Tissue prepared for transplantation is sterilized and can be processed into soft tissue or bone allografts for use in surgical reconstruction, whereas non-transplant tissue is prepared for clinical training and drug, medical device, and translational research. Xenogeneic tissue, which is most often derived from porcine or bovine sources, is also commercially available and is subject to strict regulations for animal breeding and screening for infectious diseases. Although xenogeneic products have historically been decellularized for use as non-immunogenic tissue products, recent advances in gene editing have opened the door to xenograft organ transplants into human patients. Herein, we describe an overview of the modern sourcing, regulation, processing, and applications of tissue products relevant to the field of plastic and reconstructive surgery.

Vascular allografts for clinical application in Europe: assessment of 30 years of experience with vascular tissue banking in Brussels.

Vascular tissue banking has been carried out in Brussels for over 30 years in compliance with EU and Swiss tissue banking regulations. A total of 2.765 vascular tissue donations were performed in Belgian, French, Netherlands and Suisse transplant centres: 547(20%), 1.013(37%) and 1.205(43%) during the first, second and third periods, respectively. 85% and 18% increase in donations during the second and third decades compared to previous one, were remarkable. Of the 7.066 evaluated vascular tissues, 2.407(227, 921 and 1.259) were discarded (34.1%), whereas 4.659(523, 1.861 and 2.275) accepted (65.9%) during the respective period. Of the 92 donated veins, 44(47.8%) were discarded and 48(52.2%) accepted. Allografts available for clinical application were stored in vapours of liquid nitrogen. A total of 4.636 allografts were delivered and transplanted for cases of infection (58%), critical limb ischaemia (16%) and congenital cardiac surgery (15%). Thirty veins were implanted. The progressive increases in donations of 20%, 37% and 43% and in transplantations of 20.8%, 34.6% and 45% during the first, second and third periods, respectively, were remarkable. Complications were reported after transplantation and these included acute rejection of two femoral arteries one month after transplantation. We conclude that the donation and transplantation of cryopreserved vascular allografts was stable with a progressive increase over time. Allografts were used predominantly for the treatment of infection, limb salvage for critical ischaemia and for neonates and infants with congenital cardiac malformation. Immune related rejection was observed. This should be a subject of future investigation.

Impact of Washing Processes on RNA Quantity and Quality in Patient-Derived Colorectal Cancer Tissues.

Background: Colorectal cancer (CRC) is a common and lethal cancer worldwide. Extraction of high-quality RNA from CRC samples plays a key role in scientific research and translational medicine. Specimen collection and washing methods that do not compromise RNA quality or quantity are needed to ensure high quality specimens for gene expression analysis and other RNA-based downstream applications. We investigated the effect of tissue specimen collection and different preparation processes on the quality and quantity of RNA extracted from surgical CRC tissues. Materials and Methods: After surgical resection, tissues were harvested and prepared with various washing processes in a room adjacent to the operating room. One hundred fourteen tissues from 36 CRC patients were separately washed in either cold phosphate-buffered saline reagent (n = 34) or Dulbecco's modified Eagle's medium (DMEM; n = 34) for 2-3 minutes until the stool was removed, and unwashed specimens served as controls (n = 34). Six tissue specimens were washed and immersed in DMEM for up to 1 hour at 4°C. Before RNA extraction, all specimens were kept in the stabilizing reagent for 3 months at -80°C. RNA was extracted, and the concentration per milligram of tissue was measured. RNA quality was assessed using the RNA integrity number (RIN) value. Results: Different washing processes did not result in significant differences in RNA quantity or RIN values. In the six tissues that were washed and immersed in DMEM for 1 hour, RIN values significantly decreased. The quality of the extracted RNA from most specimens was excellent with the average RIN greater than 7. Conclusions: RNA is stable in specimens washed in different processes for short periods, but RIN values may decrease with prolonged wash times.

Application of tumoroids derived from advanced colorectal cancer patients to predict individual response to chemotherapy.

Therapeutic approaches of advanced colorectal cancer are more complex, here we present a living biobank of patient-derived tumoroids from advanced colorectal cancer patients and show examples of how these tumoroids can be used to to simulate cancer behavior ex vivo and provide more evidence for tumoroids could be utilized as a predictive platform during chemotherapy treatment to identify the chemotherapy response. Morphological, histological and genomic characterization analysis of colorectal cancer tumoroids was conducted. Further, we treated colorectal cancer tumoroids with different drugs to detect cellular activities to evaluate drug sensitivity using CellTiter-Glo 3 D cell viability assay. Then the drug sensitivity of tumoroids was compared with clinical outcomes. Our results implied that tumoroids recapitulated the histological features of the original tumours and genotypic profiling of tumoroids showed a high-level of similarity to the matched primary tumours. Dose-response curves, area under the curve and tumour inhibitory rate of each therapeutic profiling calculations in tumoroids demonstrated a great diversity and we gained 88.24% match ratio between the sensitivity data of tumoroids with their paired patients' clinical outcomes. tumour inhibitory rate of each treatment parameters in tumoroids performed positive correlation with progression-free survival while area under the curve of each treatment parameters performed negative correlation with progression-free survival of the corresponding patients. In summary, We presented a living biobank of tumoroids from advanced colorectal cancer patients and show tumoroids got great potential for predicting clinical responses to chemotherapy treatment of advanced colorectal cancer.

Resultados post operatorios en pacientes con prótesis total de revisión de cadera mas injerto óseo cadavérico de banco de tejidos en el Hospital de Clínicas en el periodo 2017 al 2020 / Postoperative results in patients with total hip revision arthroplasty and cadaveric bone graft of tissue bank at the Hospital de Clínicas in the period 2017 to 2020

Introducción: La artroplastia total de cadera de revisión junto con la utilización de injerto óseo cadavérico de banco de tejidos es una alternativa de tratamiento eficaz ante los procedimientos de reemplazo con déficit óseo femoral o acetabular. El presente estudio, analizó los resultados post operatorios en pacientes intervenidos quirúrgicamente en el Hospital de Clínicas. Materiales y métodos: Estudio descriptivo. Muestreo no probabilístico de casos consecutivos atendidos en la Cátedra de Ortopedia y Traumatología de la Facultad de Ciencias Médicas (U.N.A). Fueron captados pacientes con indicación de artroplastia total de cadera de revisión (ATCR) más injerto óseo cadavérico de banco de tejidos, entre diciembre 2017 - octubre 2020, previo consentimiento informado. Se relevaron datos cuya caracterización fue posible mediante un instrumento establecido previamente, ingresado en base Excel. Resultados: 12 pacientes con déficit óseo femoral y acetabular han sido tratados con artroplastia total de cadera de revisión más injerto óseo cadavérico de banco de tejidos, en donde además de la funcionalidad y a través de seguimientos radiológicos se ha determinado la osteointegración total de los aloinjertos. La relación masculino-femenina fue 1/1, siendo el diagnóstico preoperatorio para la colocación de la prótesis de revisión más injerto óseo cadavérico de banco de tejidos el aflojamiento séptico en un 75%. El motivo de consulta más frecuente fue dolor y la secreción y el tiempo quirúrgico fue en promedio de 116 minutos. Conclusión: La artroplastia total de cadera de revisión más aloinjerto presenta óptimos resultados en relación a la osteointegración total y funcionalidad.

Introduction: Revision total hip arthroplasty with use of cadaveric bone graft is an effective treatment for replacement procedures in patients with bone loss femoral or acetabular. The present study analyzed the postoperative results in patients who underwent surgery at the Hospital de Clínicas. Materials and methods: Descriptive study. Non-probabilistic sampling of consecutive cases treated at the Department of Orthopedics and Traumatology of Hospital de Clínicas. Data of patients with indication for revision total hip arthroplasty plus cadaveric bone graft from a tissue bank with prior informed consent,were analyzed between December 2017 and October 2020. Results: 12 patients with femoral and acetabular bone deficits have been treated with revision total hip arthroplasty plus cadaveric bone graft from a tissue bank. A radiological and functional follow up was made. The male-female ratio was 1/1, with the preoperative diagnosis for placement of the revision prosthesis plus cadaveric bone graft,from the tissue bank,was septic loosening in 75%. The most frequent symptom was pain, all revision total hip arthroplasties were performed through a posterior approach, and the surgical time was an average of 116 minutes,using a later approach in all cases.Two intraoperative fracture was presented, and were resolved. Conclusion: Revision total hip arthroplasty plus allograft presents optimal results in relation to total osseointegration and functionality.

Ovarian tissue bank for fertility preservation and anti-menopause hormone replacement.

Traditional fertility preservation methods such as embryo or oocyte cryopreservation cannot meet the needs of a cancer patient or for personal reasons. The cryopreservation of ovarian tissue can be an alternative and has become a hot spot to preserve fertility or hormone replacement. The freezing of ovarian tissue can be carried out at any time without ovarian hyperstimulation to retrieve follicles. It is an ideal strategy to preserve reproductive function in children, adolescent cancer patients, and patients who are in urgent need of cancer treatment. With the increasing demands of women with premature ovarian failure or in menopause, ovarian tissue transplantation is also an alternative for hormone replacement that can provide physiological doses of hormone levels, which can avoid a series of risks such as thrombosis, breast cancer, or other hormone-dependent tumors, caused by oral hormone replacement. Hence, ovarian tissue banking can be regarded as a mainstream strategy for fertility preservation and anti-menopause hormone replacement in further clinical investigation.

[Quality assurance in tissue biobanking-an overview]. / Qualitätssicherung im Gewebebiobanking ­ Ein Überblick.

Tissue biobanks are important resource and technology platforms for biomedical research, which deals with molecular pathogenesis and the prevention, diagnosis and treatment of diseases.Due to this central role in the standardised collection, storage and distribution of human tissue and its derivatives, a practised quality management is one of the most important measures to achieve and maintain a comprehensive quality assurance of all biobanking processes. At the same time, this promotes acceptance and credibility. External quality assurance of biobanks can be achieved through accreditation. Within the German biobanking community, increasing harmonisation of biobanking processes has also been achieved through the provision of various quality assurance measures by the German Biobank Node (GBN).In the following, challenges and opportunities in the implementation of a comprehensive quality assurance in biobanking will be discussed and solutions for tissue biobanking will be presented using the example of the tissue bank of the National Centre for Tumour Diseases (NCT).

Testicular Tissue Banking for Fertility Preservation in Young Boys: Which Patients Should Be Included?

Due to the growing number of young patients at risk of germ cell loss, there is a need to preserve spermatogonial stem cells for patients who are not able to bank spermatozoa. Worldwide, more and more clinics are implementing testicular tissue (TT) banking programs, making it a novel, yet indispensable, discipline in the field of fertility preservation. Previously, TT cryopreservation was predominantly offered to young cancer patients before starting gonadotoxic chemo- or radiotherapy. Nowadays, most centers also bank TT from patients with non-malignant conditions who need gonadotoxic conditioning therapy prior to hematopoietic stem cell (HSCT) or bone marrow transplantation (BMT). Additionally, some centers include patients who suffer from genetic or developmental disorders associated with prepubertal germ cell loss or patients who already had a previous round of chemo- or radiotherapy. It is important to note that the surgical removal of TT is an invasive procedure. Moreover, TT cryopreservation is still considered experimental as restoration methods are not yet clinically available. For this reason, TT banking should preferably only be offered to patients who are at significant risk of becoming infertile. In our view, TT cryopreservation is recommended for young cancer patients in need of high-risk chemo- and/or radiotherapy, regardless of previous low-risk treatment. Likewise, TT banking is advised for patients with non-malignant disorders such as sickle cell disease, beta-thalassemia, and bone marrow failure, who need high-risk conditioning therapy before HSCT/BMT. TT retrieval during orchidopexy is also proposed for patients with bilateral cryptorchidism. Since patients with a medium- to low-risk treatment generally maintain their fertility, TT banking is not advised for this group. Also for Klinefelter patients, TT banking is not recommended as it does not give better outcomes than a testicular sperm extraction later in life.

Impact of Sars-CoV-2 pandemic on the Veneto Region multitissue bank activity.

Covid pandemic affected donation activities worldwide, especially for living donation due to the lack of elective surgery. Moreover, the number of heart-beating and non-heart beating donors has recorded a decrease. Fondazione Banca dei Tessuti di Treviso (FBTV) is a non-profit healthcare organisation, located in Veneto Region, tasked with procurement, processing, preserving, validating and distributing human tissue for clinical use. During Covid-19 outbreak, operations in FBTV have never stopped and a great effort was required to maintain a standard trend of activity. The aim of this study was to describe the impact of Sars-CoV-2 on the activity of a multitissue bank in Italy. Moreover, we investigated the presence of the virus in tissues retrieved from two Sars-CoV-2 positive cadaver donors. Our survey demonstrated that the transplantation network of Veneto Region has positively reacted to the pandemic scenario, thanks to the effort of all personnel involved. Statistical analyses underlined that most of the activities of the tissue bank were unaffected during the Sars-CoV-2 pandemic.

Ten-year experience with cryopreserved vascular allografts in the Croatian Cardiovascular Tissue Bank.

The Croatian Cardiovascular Tissue Bank (CTB) was established in June 2011. Activities managed by CTB are processing of heart valves and blood vessels, as well as quality control, storage, medical release and distribution of allografts. The aim of this report is to present CTB's vascular tissue activities and retrospectively evaluate the outcomes of their use in the University Hospital Centre Zagreb. Between June 2011 and July 2021, 90 vascular allografts (VAs) from 55 donors after brain death were referred to CTB. Only 54% of VAs met the tissue quality requirements while 46% of tissues were discarded. The most frequent reasons for discard were unacceptable morphology and initial microbiological contamination. Altogether 42 VAs were released for transplantation and 37 of them were used in 27 surgical procedures. The most common indication for surgery was prosthetic graft or stent infection. According to the anatomic position of vascular reconstruction, patients were divided in the aortic and peripheral reconstruction group. A total of 23 patients were treated. In the aortic reconstruction group 58% of patients did not experience any graft-related complications. In the group of patients who underwent peripheral reconstruction significant incidence of reinfection was observed highlighting it as a major graft-related complication. Despite the small patient groups and limited duration of follow-up, presented clinical outcomes provide valuable information on the efficacy of vascular allografts. Additional clinical results collected on a larger patient groups and comparison to other reconstructive treatment options are necessary.

The potential of radiation sterilized and banked tissue allografts for management of nuclear casualties.

Processed and radiation sterilized allograft tissues that can be banked for use on demand are a precious therapeutic resource for the repair or reconstruction of damaged or injured tissues. Skin dressings or skin substitutes like allograft skin, amniotic membrane and bioengineered skin can be used for the treatment of thermal burns and radiation induced skin injuries. Bone grafts can be employed for repairing fracture defects, filling in destroyed regions of bone, and treatment of spinal and joint injuries. A nuclear scenario would result in a large number of casualties due to the heat, blast and radiation effects of the weapon. Perspective of radiation sterilized biological tissues provided by the tissue banks for management of casualties in a nuclear disaster scenario is presented.

Systematic review and meta-analysis of the papillomavirus prevalence in breast cancer fresh tissues.

BACKGROUND: Although widely studied, the role of HPV in the genesis of breast carcinomas remains elusive due to the diversity of results across studies, possibly caused by the wide methodological heterogeneity, some of them with inadequate methods. OBJECTIVE: To verify the association between HPV and breast cancer through the meta-analysis of studies that used the best-recognized techniques for viral detection and tissue conservation. METHODS: A systematic review and meta-analysis restricted to studies that detected HPV by PCR in fresh and frozen tissue from breast cancer were conducted to obtain greater homogeneity. PubMed, Scopus, Science Direct, Cochrane Library, and SciELO were searched until December 14, 2019. Search terms included "breast cancer" and "HPV" without language restrictions. Eleven studies were included in the meta-analysis. The pooled relative risks and 95% confidence interval (95% CI) were calculated, and heterogeneity was assessed using the I-squared (I2). RESULTS: The selected studies had very low heterogeneity (2%). There is a 2.15 times higher combined relative risk (95% CI = 1.60-2.89) of detecting HPV in breast cancer than in cancer-free breast controls with a statistically significant p-value (p < 0.0001). CONCLUSION: Our data support the association of DNA-HPV with breast carcinomas. Further studies are needed to find out which breast cancer subtypes this association is most frequent.

A method for rapid flow-cytometric isolation of endothelial nuclei and RNA from archived frozen brain tissue.

Endothelial cells are important contributors to brain development, physiology, and disease. Although RNA sequencing has contributed to the understanding of brain endothelial cell diversity, bulk analysis and single-cell approaches have relied on fresh tissue digestion protocols for the isolation of single endothelial cells and flow cytometry-based sorting on surface markers or transgene expression. These approaches are limited in the analysis of the endothelium in human brain tissues, where fresh samples are difficult to obtain. Here, we developed an approach to examine endothelial RNA expression by using an endothelial-specific marker to isolate nuclei from abundant archived frozen brain tissues. We show that this approach rapidly and reliably extracts endothelial nuclei from frozen mouse brain samples, and importantly, from archived frozen human brain tissues. Furthermore, isolated RNA transcript levels are closely correlated with expression in whole cells from tissue digestion protocols and are enriched in endothelial markers and depleted of markers of other brain cell types. As high-quality RNA transcripts could be obtained from as few as 100 nuclei in archived frozen human brain tissues, we predict that this approach should be useful for both bulk analysis of endothelial RNA transcripts in human brain tissues as well as single-cell analysis of endothelial sub-populations.

Guidelines for Biobanking of Bone Marrow Adipose Tissue and Related Cell Types: Report of the Biobanking Working Group of the International Bone Marrow Adiposity Society.

Over the last two decades, increased interest of scientists to study bone marrow adiposity (BMA) in relation to bone and adipose tissue physiology has expanded the number of publications using different sources of bone marrow adipose tissue (BMAT). However, each source of BMAT has its limitations in the number of downstream analyses for which it can be used. Based on this increased scientific demand, the International Bone Marrow Adiposity Society (BMAS) established a Biobanking Working Group to identify the challenges of biobanking for human BMA-related samples and to develop guidelines to advance establishment of biobanks for BMA research. BMA is a young, growing field with increased interest among many diverse scientific communities. These bring new perspectives and important biological questions on how to improve and build an international community with biobank databases that can be used and shared all over the world. However, to create internationally accessible biobanks, several practical and legislative issues must be addressed to create a general ethical protocol used in all institutes, to allow for exchange of biological material internationally. In this position paper, the BMAS Biobanking Working Group describes similarities and differences of patient information (PIF) and consent forms from different institutes and addresses a possibility to create uniform documents for BMA biobanking purposes. Further, based on discussion among Working Group members, we report an overview of the current isolation protocols for human bone marrow adipocytes (BMAds) and bone marrow stromal cells (BMSCs, formerly mesenchymal), highlighting the specific points crucial for effective isolation. Although we remain far from a unified BMAd isolation protocol and PIF, we have summarized all of these important aspects, which are needed to build a BMA biobank. In conclusion, we believe that harmonizing isolation protocols and PIF globally will help to build international collaborations and improve the quality and interpretation of BMA research outcomes.

The MURAL collection of prostate cancer patient-derived xenografts enables discovery through preclinical models of uro-oncology.

Preclinical testing is a crucial step in evaluating cancer therapeutics. We aimed to establish a significant resource of patient-derived xenografts (PDXs) of prostate cancer for rapid and systematic evaluation of candidate therapies. The PDX collection comprises 59 tumors collected from 30 patients between 2012-2020, coinciding with availability of abiraterone and enzalutamide. The PDXs represent the clinico-pathological and genomic spectrum of prostate cancer, from treatment-naïve primary tumors to castration-resistant metastases. Inter- and intra-tumor heterogeneity in adenocarcinoma and neuroendocrine phenotypes is evident from bulk and single-cell RNA sequencing data. Organoids can be cultured from PDXs, providing further capabilities for preclinical studies. Using a 1 x 1 x 1 design, we rapidly identify tumors with exceptional responses to combination treatments. To govern the distribution of PDXs, we formed the Melbourne Urological Research Alliance (MURAL). This PDX collection is a substantial resource, expanding the capacity to test and prioritize effective treatments for prospective clinical trials in prostate cancer.

Breast cancer biobank from a single institutional cohort in an urban setting in india: Tumor characteristics and survival outcomes.

BACKGROUND: A breast cancer biobank with retrospectively collected patient data and FFPE tissue samples was established in 2018 at Prashanti Cancer Care Mission, Pune, India. It runs a cancer care clinic with support from a single surgeon's breast cancer practice. The clinical data and tissue sample collection is undertaken with appropriate patient consent following ethical approval and guidelines. METHODS: The biobank holds clinical history, diagnostic reports, treatment and follow-up information along with FFPE tumor tissue specimens, adjacent normal and, in few cases, contralateral normal breast tissue. Detailed family history and germline mutational profiles of eligible and consenting patients and their relatives are also deposited in the biobank. RESULTS: Here, we report the first audit of the biobank. A total number of 994 patients with breast disease have deposited consented clinical records in the biobank. The majority of the records (80%, n = 799) are of patients with infiltrating ductal carcinoma (IDC). Of 799 IDC patients, 434 (55%) have deposited tumor tissue in the biobank with consent. In addition, germline mutation profiles of 84 patients and their family members are deposited. Follow-up information is available for 85% of the 434 IDC patients with an average follow-up of 3 years. CONCLUSION: The biobank has aided the initiation of translational research at our center in collaboration with eminent institutes like IISER Pune and SJRI Bangalore to evaluate profiles of breast cancer in an Indian cohort. The biobank will be a valuable resource to the breast cancer research community, especially to understand South Asian profiles of breast cancer.

Integrated Whole-Exome and Transcriptome Sequencing of Sporadic Parathyroid Adenoma.

Purpose: Hyperparathyroidism is the third most common endocrine disease. Parathyroid adenoma (PA) accounts for approximately 85% of cases of primary hyperparathyroidism, but the molecular mechanism is not fully understood. Herein, we aimed to investigate the genetic and transcriptomic profiles of sporadic PA. Methods: Whole-exome sequencing (WES) and transcriptome sequencing (RNA-seq) of 41 patients with PA and RNA-seq of 5 normal parathyroid tissues were performed. Gene mutations and characterized expression changes were identified. To elucidate the molecular mechanism underlying PA, unsupervised consensus clustering of RNA-seq data was performed. The correlations between the sequencing data and clinicopathological features of these patients were analyzed. Results: Previously reported PA driver gene mutations, such as MEN1 (9/41), mTOR (4/41), ZFX (3/41), CASR (3/41), EZH2 (2/41) and FAT1 (2/41), were also identified in our cohort. Furthermore, somatic mutation of EZH1, which had not been reported in PA, was found in 4 samples. RNA-seq showed that the expression levels of 84 genes were upregulated and 646 were downregulated in PA samples compared with normal samples. Unsupervised clustering analysis of RNA-seq data clustered these patients into 10 subgroups related to mutation or abnormal expression of a group of potential pathogenic genes. Conclusion: MEN1, EZH2, CASR, EZH1, ZFX, mTOR and FAT1 mutations in PA were revealed. According to the RNA-seq data clustering analysis, cyclin D1, ß-catenin, VDR, CASR and GCM2 may be important factors contributing to the PA gene expression profile.