Endocrine tumors, next generation sequencing

BACKGROUND: Penile squamous cell carcinoma (PSCC) is a rare disease that is more prevalent in developing countries, such as Brazil, and is linked to poor genital hygiene, which promotes the proliferation of microorganisms. Dysbiosis has an effect on the local immune response, increases the risk of viral infection, and can generate inflammatory processes. Current knowledge of the microbiota found in penile tissues is limited, and the bacterial diversity of the PSCC remains unknown. In this investigation, the microbiota associated with penile cancer and its potential role in tumor development and progression were identified...

BACKGROUND: although being central for the biology and druggability of hormone-receptor positive, HER2 negative metastatic breast cancer (MBC), ESR1 and PIK3CA mutations are simplistically dichotomized as mutated or wild type in current clinical practice. METHODS: The study analyzed a multi-institutional cohort comprising 703 patients with luminal-like MBC characterized for circulating tumor DNA through next generation sequencing (NGS). Pathway classification was defined based on previous work (i...

Thyroid cancer is associated with a broad range of different mutations, including RET fusion genes. The importance of characterizing RET fusion-positive tumors has recently increased due to the possibility of targeted treatment. The aim of this study was to identify RET fusion-positive thyroid tumors, correlate them with clinicopathological features, compare them with other mutated carcinomas, and evaluate long-term follow-up of patients. The cohort consisted of 1564 different thyroid tissue samples (including 1164 thyroid carcinoma samples) from pediatric and adult patients...

BACKGROUND: There is increasing interest in the use of liquid biopsies, but data on longitudinal analyses of circulating tumor DNA (ctDNA) remain relatively limited. Here, we report a longitudinal ctDNA analysis of MONALEESASIA, a phase Ib trial evaluating the efficacy and safety of ribociclib plus endocrine therapy (ET) in Asian patients with hormone receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer. METHODS: MONALEESASIA enrolled premenopausal and postmenopausal Japanese and postmenopausal non-Japanese Asian patients...

INTRODUCTION: Von Hippel Lindau (VHL) syndrome is caused by an autosomal dominant hereditary or sporadic germline mutation of the VHL gene with more than five hundred pathogenic mutations identified. Pheochromocytomas and rarely paragangliomas occur in 10-50% of patients with VHL syndrome usually around 30 years of age and exceptionally before the age of 10. CASE PRESENTATION: We diagnosed a 9-year-old girl of normal appearance and severe refractory hypertension, with a norepinephrine-secreting pheochromocytoma related to VHL syndrome due to a known familial germline heterozygous mutation of VHL gene (c...

PURPOSE: Adrenal schwannoma (AS) and periadrenal schwannoma (PAS) are exceedingly rare Schwann cell tumors that develop from the adrenal medulla and periadrenal peripheral nerves respectively. The underlying genetic events are elusive. METHODS: We searched our institutional database for AS/PAS cases and reviewed the histology and clinical outcome. Comprehensive molecular work-up was performed. RESULTS: We found reports of 4 AS/PAS cases diagnosed between 1992 and 2022 among the 1248 adrenal lesions submitted for histopathology during the same time period (0...

BACKGROUND: The incidence of thyroid cancer in China has rapidly increased in recent decades. As the genetic profiles of thyroid cancer vary dramatically between different geographical regions, a comprehensive genetic landscape of thyroid cancer in the Chinese population is urgently needed. METHODS: We retrospectively included thyroid cancer patients from three Chinese medical centers between February 2015 and August 2020. To dissect the genomic profiling of these patients, we performed targeted next-generation sequencing on their tumor tissues using a 1,021-gene panel...

The treatment of advanced, radioiodine refractory, differentiated thyroid cancers (RR-DTCs) has undergone major advancements in the last decade, causing a paradigm shift in the management and prognosis of these patients. Better understanding of the molecular drivers of tumorigenesis and access to next generation sequencing of tumors have led to the development and Food and Drug Administration (FDA)-approval of numerous targeted therapies for RR-DTCs, including antiangiogenic multikinase inhibitors, and more recently, fusion-specific kinase inhibitors such as RET inhibitors and NTRK inhibitors...

PURPOSE OF REVIEW: To summarize recent developments in the diagnosis and management of patients with anaplastic thyroid cancer (ATC). RECENT FINDINGS: An updated edition of the Classification of Endocrine and Neuroendocrine Tumors was released by the World Health Organization (WHO), in which squamous cell carcinoma of the thyroid are now a subtype of ATC. Broader access to next generation sequencing has allowed better understanding of the molecular mechanisms driving ATC and improved prognostication...

Nineteen cases of parathyroid carcinoma in patients with multiple endocrine neoplasia type 1 have been reported in the literature, of which eleven carry an inactivating germline mutation in the MEN1 gene. Somatic genetic abnormalities in these parathyroid carcinomas have never been detected. In this paper, we aimed to describe the clinical and molecular characterization of a parathyroid carcinoma identified in a patient with MEN1. A 60-year-old man was diagnosed with primary hyperparathyroidism during the postoperative period of lung carcinoid surgery...

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology , to patients seen in their own clinical practice...

Low-grade serous ovarian cancer was initially described as a distinct type of rare epithelial ovarian cancer 20 years ago; however, only recently have physicians begun to leverage the understanding of the clinical behavior and molecular profile of this disease for treatment. The use of routine next-generation sequencing has allowed a deeper understanding of the molecular drivers of this disease and shown how molecular alterations in mitogen-activated protein kinase pathway genes such as KRAS and BRAF can affect overall prognosis and disease behavior...

PURPOSE: How to factor both tumor burden and oncogenic genomic mutations as variables to predict the outcome of endocrine-based therapy (ET) in ER-positive/HER2-negative metastatic breast cancer patients (MBC) remains to be explored. METHOD: Blood samples prospectively collected from 163 ER-positive/HER2-negative female MBC patients, before ET, were used for cell-free tumor DNA (cfDNA) analysis. cfDNA was subjected to next-generation sequencing (NGS) to interrogate oncogenic PIK3CA hotspot and TP53 DNA-binding domain (DBD) mutations, including single nucleotide variants (SNVs) or small insertions and deletions (InDels)...

OBJECTIVES: To present a case of a new pathogenic variant of DICER1. CASE PRESENTATION: 13-year-old female with non-toxic multinodular goiter and ovarian Sertoli-Leydig cell tumor, in whom a pineal parenchymal tumor of intermediate differentiation was diagnosed. Next-generation sequencing revealed a new germline mutation in the DICER1 gene (exon 16, c2488del [pGlu830Serfs*2] in heterozygosis), establishing the diagnosis of DICER1 syndrome. CONCLUSIONS: Mutations in the DICER1 gene cause genetic predisposition to a wide spectrum of benign or malignant tumors from childhood to adulthood...

A 44-year-old female patient with a familial adenomatous polyposis (FAP) was diagnosed with a cribriform morular thyroid carcinoma (CMTC). We observed within the very necrotic tumor a small but distinct poorly differentiated carcinomatous component. As expected, next generation sequencing of both components revealed a homozygous APC mutation and in addition, a TERT promoter mutation. A TP53 mutation was found exclusively in the CMTC part, while the poorly differentiated component showed a clonal evolution, harboring an activating PIK3CA mutation and copy number gains of BRCA2, FGF23, FGFR1, and PIK3CB-alterations which are typically seen in squamous cell carcinoma...

BACKGROUND: Endocrine-resistant HR+/HER2- breast cancer (BC) and triple-negative BC (TNBC) are of interest for molecularly informed treatment due to their aggressive natures and limited treatment profiles. Patients of African Ancestry (AA) experience higher rates of TNBC and mortality than European Ancestry (EA) patients, despite lower overall BC incidence. Here, we compare the molecular landscapes of AA and EA patients with HR+/HER2- BC and TNBC in a real-world cohort to promote equity in precision oncology by illuminating the heterogeneity of potentially druggable genomic and transcriptomic pathways...

BACKGROUND: ESR1 mutations have been identified as mechanism for endocrine resistance and are also associated with a decreased overall survival. We assessed ESR1 mutations in circulating tumor DNA (ctDNA) for impact on outcome to taxane-based chemotherapy in advanced breast cancer patients. METHODS: ESR1 mutations were determined in archived plasma samples from patients treated with paclitaxel and bevacizumab (AT arm, N = 91) in the randomized phase II ATX study...

OBJECTIVE: 20% of sporadic MTC has no RET/RAS somatic alterations or other known gene alterations. Aim of this study was to investigate RET/RAS negative MTC for the presence of NF1 alterations. METHODS: we studied 18 sporadic RET/RAS negative MTC cases: Next generation sequencing of tumoral and blood DNA was performed using a custom panel including the entire coding region of the NF1 gene. The effect of NF1 alterations on the transcripts were characterized by RT-PCR and the loss of heterozygosity of the other NF1 allele was investigated with Multiplex Ligation-dependent Probe Amplification...

Endocrine therapy (ET) is the cornerstone of management in hormone receptor (HR)+ breast cancer (BC). Indeed, targeting the estrogen receptor (ER) signaling at different levels is a successful strategy, since BC largely relies on the ER signaling as a driver of tumorigenesis and progression. In metastatic BC, progression of disease typically occurs due to either ligand-independent ER signaling, which favors tumor proliferation and survival in the absence of hormonal stimuli, or an ER-independent signaling, which exploits alternative transcription pathways...

Thymic neuroendocrine tumors associated with multiple endocrine neoplasia are only defined as carcinoid and are not associated with large-cell neuroendocrine carcinoma (LCNEC). We report the case of a multiple endocrine neoplasia type 1 patient with atypical carcinoid tumors with elevated mitotic counts (AC-h), an intermediate condition between carcinoid and LCNEC. A 27-year-old man underwent surgery for an anterior mediastinal mass and was diagnosed with thymic LCNEC. Fifteen years later, a mass appeared at the same site, which was determined to be a postoperative recurrence based on the pathological results of a needle biopsy and the clinical course...