A5050618133- Adrenal and Paraganglionic Tumors
- Thyroid Cancer Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- Hormonal Regulation and Hypertension
- BRCA gene mutations in cancer
- Neuroblastoma Research and Treatments
- Glioma Diagnosis and Treatment
- Genetic factors in colorectal cancer
- Radiopharmaceutical Chemistry and Applications
- Neuroendocrine Tumor Research Advances
- Pituitary Gland Disorders and Treatments
- Chemical Reactions and Isotopes
- Congenital Diaphragmatic Hernia Studies
- Neurofibromatosis and Schwannoma Cases
- Head and Neck Anomalies
- Ovarian cancer diagnosis and treatment
- Cancer-related Molecular Pathways
- Ferroptosis and cancer prognosis
- FOXO transcription factor regulation
- Urinary and Genital Oncology Studies
- Neonatal Respiratory Health Research
- Mitochondrial Function and Pathology
- Cancer Diagnosis and Treatment
- Telomeres, Telomerase, and Senescence
- Virus-based gene therapy research
Karolinska University Hospital
2016-2025
Karolinska Institutet
2015-2024
Swedish School of Sport and Health Sciences
2017
Yale University
2017
Anaplastic thyroid carcinoma (ATC) is a frequently lethal malignancy that often unresponsive to available therapeutic strategies. The tumorigenesis of ATC and its relationship the widely prevalent well-differentiated carcinomas are unclear. We have analyzed 22 cases as well 4 established cell lines using whole-exome sequencing. A total 2674 somatic mutations (121/sample) were detected. Ontology analysis revealed majority variants aggregated in MAPK, ErbB RAS signaling pathways. Mutations...
Effective cancer prevention is based on accurate molecular diagnosis and results of genetic family screening, genotype-informed risk assessment, tailored strategies for early diagnosis. The expanding etiology hereditary pheochromocytomas paragangliomas has recently included SDHA, TMEM127, MAX, SDHAF2 as susceptibility genes. Clinical management guidelines patients with germline mutations in these 4 newly genes are lacking.To study the clinical spectra age-related penetrance individuals...
Adrenocortical carcinoma (ACC) is a rare and lethal malignancy with poorly defined etiology, the molecular genetics of ACC are incompletely understood.To utilize whole-exome sequencing for genetic characterization underlying somatic mutations copy number alterations present in ACC.Screening mutation events (CNAs) was performed by comparative analysis tumors matched normal samples from 41 patients ACC.In total, 966 nonsynonymous were detected, including 40 mean 16 per sample one tumor 314...
Abstract Anaplastic thyroid cancer (ATC) is a rare but severe form of responsible for approximately 50% deaths. Consequently, the identification innovative therapies remains crucial effective treatment ATC. Molecular radiotherapy rapidly growing field within oncology and cell surface antigen CD44v6, which overexpressed in several cancers, plausible target molecular Immunohistochemistry (IHC) 39 ATC patient samples were evaluated CD44v6 expression. Biodistribution dosimetry 125I/177Lu-labeled...
As subsets of pheochromocytomas (PCCs) lack a defined molecular etiology, we sought to characterize the mutational landscape PCCs identify novel gene candidates involved in disease development. A discovery cohort 15 wild type for mutations PCC susceptibility genes underwent whole‐exome sequencing, and an additional 83 served as verification targeted sequencing candidate mutations. low rate nonsilent single nucleotide variants (SNVs) was detected (6.1/sample). Somatic HRAS EPAS1 were observed...
DICER1 germline mutations cause syndrome, in which multinodular goitre is a common feature. Recently, somatic have been reported sporadic thyroid carcinomas, of the newly described macrofollicular variant follicular carcinoma (MV-FTC) seems particularly enriched for this aberrancy. We report here histological and genetic findings five tumours with architecture (four carcinomas one adenoma).We diagnosed cases during year-long period at Karolinska University Hospital, tertiary cancer center...
Follicular thyroid tumors pose a diagnostic challenge on the preoperative level, as discrimination between follicular carcinoma (FTC) and adenoma (FTA) demands careful histopathological investigation. Moreover, prognostication of FTCs is mostly based tumor size extent invasive properties, while immunohistochemical markers pinpointing high-risk cases are lacking. We have routinely established Ki-67 labeling index for since 1999. To assess potential value an adjunct tool to (1) correctly...
Abstract Somatic and biallelic DICER1 mutations are reported in subsets of thyroid tumors, supporting the role this gene tumor development. As recent studies have brought attention to macrofollicular patterns, atrophic changes, papillary structures as being associated with mutations, we sought explore these observations a bi-institutional cohort. A total 61 lesions (54 tumors 7 cases follicular nodular disease; TFND), including 26 mutated 35 wildtype controls were subjected histological...
Abstract The genetics underlying thyroid cancer dedifferentiation is only partly understood and has not yet been characterised using comprehensive pan‐genomic analyses. We investigated a unique case with synchronous follicular carcinoma (FTC), poorly differentiated (PDTC), anaplastic (ATC), as well regional lymph node metastases from the PDTC ATC single patient whole‐genome sequencing (WGS). FTC displayed mutations in CALR , RB1 MSH2 exhibited TP53 DROSHA APC TERT additional DNA repair genes...
Mutations of the Telomerase reverse transcriptase (TERT) gene promoter are recurrently found in follicular thyroid carcinoma (FTC) and tumors uncertain malignant potential (FT-UMP), but nearly never adenoma (FTA). We, therefore, believe these mutations could signify potential. At our department, postoperative TERT mutational testing FT-UMPs was implemented 2014, with a positive mutation screening leading to vigilant follow-up sometimes adjuvant treatment. To date, we screened 51 compared...
TERT promoter mutation (TERTpMut ) has a strong association to recurrence and been suggested act as driver for malignant transformation of WHO grade I II meningiomas. TERTpMut investigated in selected high-grade meningioma samples. The existence across recurrent tumors population-based cohort needs be order identify when emerges samples validate prognostic impact among III tumors.We gathered material from consecutive single-center 40 patients with (WHO III) treated between 2000 2018,...
<div>Abstract<p>Anaplastic thyroid cancer (ATC) is a rare but severe form of responsible for approximately 50% deaths. Consequently, the identification innovative therapies remains crucial effective treatment ATC. Molecular radiotherapy rapidly growing field within oncology, and cell surface antigen CD44v6, which overexpressed in several cancers, plausible target molecular IHC 39 patient samples with ATC was evaluated CD44v6 expression. Biodistribution dosimetry iodine-125...
<p>Supplemental Figure 4: Biodistribution of BHT-101 therapy mice. Left: animals carrying xenografts treated with 177Lu-UU-40 (6.5 MBq) dissected on the day termination due to reaching TBL. Right: isotype control antibody, 177Lu-B1-8 (7 MBq), TBL.</p>
<p>Supplemental Figure 3: CD44v6 antigen expression levels of BHT-101 and ACT-1. A. In vitro specificity 125I- 177Lu-UU-40 with/without 100-fold molar excess (block) unlabeled UU-40 on cells. B. ACT-1 C. IHC staining in xenografts. D. Unpaired t-tests assessed the level significance between blocked unblocked wells both radioconjugates cell lines. P < 0.0001 (****), p 0.001 (***).</p>
<p>Supplemental Table 1: Patient data from ATC IHC samples</p>
<p>Supplemental Figure 1: Representative images of IHC-stainings for CD44v6 from tumors ATC patients. Images were obtained by high resolution microscope using 400x magnification. No image-adjustments have been made. Case no T1-T39 are cross-linked with data found in Supplemental Table 1.</p>
<p>Supplemental Figure 2: Representative HPLC-SEC chromatograms of UU-40 and DOTA-UU-40 SPR sensorgrams CD44v6-binding. A. HPLC evaluation samples stored at -20C or -80C for 23 days. B. (top row) (bottom to CD44iso4-Fc (naturally occurring v6-positive CD44, Fc-fused) human v6-peptide after storage either 4C, 80C Affinity the Fc-fused CD44v6 iso4-protein should be regarded as apparent affinity due influence from avidity during measurements.</p>
Pheochromocytomas (PCCs) and abdominal paragangliomas (PGLs), collectively abbreviated PPGL, are believed to exhibit malignant potential-but only subsets of cases will display full-blown properties. The Pheochromocytoma the Adrenal Gland Scaled Score (PASS) algorithm is a proposed histologic system detect potential for aggressive behavior, but little known regarding coupling underlying molecular genetics. In this study, total 92 PPGLs, previously characterized susceptibility gene status mRNA...
Pheochromocytomas (PCC) and abdominal paragangliomas (PGL) display a highly diverse genetic background recent gene expression profiling studies have shown that PCC PGL (together PPGL) alter either kinase signaling pathways or the pseudo-hypoxia response pathway dependent of composition. Recurrent mutations in Harvey rat sarcoma viral oncogene homolog (HRAS) recently been verified sporadic PPGLs. In order to further establish HRAS mutation frequency characterize associated profiles mutated...
Mutations in the miRNA enzyme gene DICER1 have been reported several endocrine malignancies and is associated with rare tumour-predisposing syndrome. mutations subsets of follicular thyroid carcinoma (FTC), but role tumorigenesis has not extensively studied. In this study, we investigate 168 tumours an FTC cell line. We found paediatric cases a general down-regulation FTCs visualized both on mRNA protein level, especially pronounced Hürthle (HuCC). The was also evident adenomas (FTAs),...
The paucity of recurrent mutations has hampered efforts to understand and treat neuroblastoma. Alternative splicing splicing-dependent RNA-fusions represent mechanisms able increase the gene product repertoire but their role in neuroblastoma remains largely unexplored. Here we investigate presence possible roles aberrant RNA-fusion transcripts In addition, attend establish whether spliceosome can be targeted Through analysis RNA-sequenced show that elevated expression factors is a strong...
Anaplastic thyroid carcinoma (ATC) is a lethal malignancy characterized by poor response to conventional therapies. Whole-genome sequencing (WGS) analyses of this tumor type are limited, and we therefore interrogated eight ATCs using WGS RNA sequencing. Five out cases (63%) displayed cyclin-dependent kinase inhibitor 2A (CDKN2A) abnormalities, either copy number loss (n = 4) or truncating mutations 1). All four with the CDKN2A locus (encoding p16 p14arf) also exhibited neighboring CDKN2B...