Review
Endocrinology & Metabolism
Matti L. Gild, Roderick J. Clifton-Bligh, Lori J. Wirth, Bruce G. Robinson
Summary: A personalized approach to MTC management has overcome challenges through advancements in diagnostic and treatment modalities, including RET testing and novel imaging techniques. Systemic therapy for persistent and metastatic disease has greatly improved with the use of targeted kinase inhibitors such as selpercatinib and pralsetinib. This article discusses the changing paradigms in MTC patient care and the evolving management strategies for this heterogeneous malignancy.
Article
Biology
Sara Milicevic, Mateja Krajc, Ana Blatnik, Barbara Peric
Summary: The study conducted on the Slovenian MTC patient population revealed that 21.6% of the patients carry RET gene pathogenic variants. Among these patients, 62% of families had none of the associated endocrinopathies, indicating that FMTC is the most common presentation. Risk-stratified management approaches can be considered for screening PHEO and PHPT in RET pathogenic variant carriers.
Article
Oncology
Ananth Shankar, Tom Kurzawinski, Emma Ross, Sara Stoneham, Tim Beale, Ian Proctor, Tony Hulse, Kate Simpson, Mark N. Gaze, Elene Cattaneo, Evelien Gevers, Lynley Marshall, Johnathan G. Hubbard, Caroline Brain
Summary: A retrospective analysis was conducted on 6 untreated children with MEN2, showing significant decreases in serum calcitonin and CEA concentrations after treatment with Selpercatinib; children with measurable radiological disease experienced significant volume reduction; Selpercatinib demonstrated excellent therapeutic efficacy with minimal toxicity in children.
EUROPEAN JOURNAL OF CANCER
(2021)
Article
Endocrinology & Metabolism
Xiao-Ping Qi, Guo-Bing Lin, Bo Chen, Feng Li, Zhi-Lie Cao, Wei-Hui Zheng, Jian-Qiang Zhao
Summary: The study reports a Chinese patient with MEN2B and associated MMFC harboring a germline RET M918T mutation. The patient underwent total thyroidectomy and family genetics screening, with a significant drop in serum calcitonin, carcinoembryonic antigen, and thyroglobulin levels post-surgery.
ENDOCRINE METABOLIC & IMMUNE DISORDERS-DRUG TARGETS
(2021)
Review
Endocrinology & Metabolism
Francesca Orsolini, Alessandro Prete, Pierpaolo Falcetta, Domenico Canale, Fulvio Basolo, Greta Ali, Francesca Manassero, Paolo Vitti, Rossella Elisei, Eleonora Molinaro
Summary: This article reports the first known case of asymptomatic bilateral testicular metastases of medullary thyroid cancer (MTC). It highlights the importance of considering the testis as a potential metastatic site of MTC, especially in patients with advanced disease.
EUROPEAN THYROID JOURNAL
(2022)
Review
Medicine, General & Internal
Naruhito Takido, Ryusuke Saito, Kaoru Okada, Norifumi Kanai, Yoshihiro Shono, Hiroaki Mitsugashira, Muneyuki Matsumura, Kengo Sasaki, Koji Miyazawa, Atsushi Fujio, Kazuaki Tokodai, Keigo Murakami, Hironobu Sasano, Michiaki Unno, Takanori Ishida, Takashi Kamei
Summary: This study presents a rare case of tumor-to-tumor metastasis of medullary thyroid carcinoma to a paraganglioma. The patient had multiple endocrine neoplasia type 2B and had undergone total thyroidectomy 20 years before the metastasis occurred.
TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Endocrinology & Metabolism
Tim Brandenburg, Vera Tiedje, Philipp Muchalla, Sarah Theurer, Frank Weber, Kurt Werner Schmid, Henning Dralle, Dagmar Fuehrer
Summary: This study retrospectively analyzed MTC patients with continued discontinuation of vandetanib treatment in a tertiary referral endocrine tumor center. The results suggest that discontinuation of long-term vandetanib treatment with documented stable disease does not automatically result in rapid disease progression but may be followed by prolonged TKI-free stable disease in individual patients. Analysis of calcitonin and CDT during discontinuation is indicated as it will unmask tumor progression earlier than imaging. Restart with the same TKI is possible in case of progression.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Endocrinology & Metabolism
Andreas Machens, Kerstin Lorenz, Tim Brandenburg, Dagmar Fuehrer-Sakel, Frank Weber, Henning Dralle
Summary: The presentation of MEN2A has changed over time, with earlier surgical interventions and a shift towards preventative medicine. This has resulted in reduced risk and improved outcomes for patients.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2023)
Article
Endocrinology & Metabolism
Andreas Machens, Kerstin Lorenz, Frank Weber, Henning Dralle
Summary: This study aimed to determine the clinical penetrance and expression of RET missense mutations associated with MEN2A in an age-dependent manner based on parental inheritance. The results showed that offspring who inherited the trait from the father developed tumors at a significantly younger age. Parental inheritance was consistently associated with MEN2A-associated tumors, highlighting the importance of considering parental inheritance in screening and early detection of these tumors.
EUROPEAN JOURNAL OF ENDOCRINOLOGY
(2022)
Article
Oncology
Chakra Diwaker, Vijaya Sarathi, Sanjeet Kumar Jaiswal, Ravikumar Shah, Anuja Deshmukh, Anand Ebin Thomas, Gagan Prakash, Gaurav Malhotra, Virendra Patil, Anurag Lila, Nalini Shah, Tushar Bandgar
Summary: Limited data on Medullary thyroid carcinoma and associated endocrinopathies in the Indian subcontinent, emphasizing the need for early diagnosis. RET mutations were the most common cause of HMTC, with different subgroups showing varying clinical characteristics and outcomes, highlighting the importance of awareness and management strategies.
Editorial Material
Radiology, Nuclear Medicine & Medical Imaging
Martin Freesmeyer, Ulrich A. Mueller, Matthias Maennel, Gabriele Mtuka-Pardon, Philipp Seifert
Summary: This article reports a case of an 80-year-old woman with osteoporosis without fractures, asymptomatic primary hyperparathyroidism, and elevated calcitonin level. Various imaging modalities revealed a suspicious thyroid nodule and enlarged submandibular lymph nodes, which were ultimately confirmed to be a paraesophageal parathyroid adenoma. The patient underwent thyroidectomy and parathyroid adenoma excision, leading to the normalization of parathyroid hormone and calcitonin levels. Multiple endocrine neoplasia IIa syndrome was suspected.
CLINICAL NUCLEAR MEDICINE
(2022)
Editorial Material
Medicine, General & Internal
Lan Chen, Jing-Xin Zhang, Dong-Ge Liu, Hong-Gang Liu
Summary: This paper presents a rare case of multiple endocrine neoplasia type 2A (MEN2A) syndrome spanning three generations in a family. The disease went undetected until a recent fine needle aspiration revealed metastasized lymph node from the son, leading to a review and correction of previously wrong diagnoses. Further molecular study revealed a RET germline mutation in family members with and without the disease. The importance of suspicion, surveillance, and a tri-level methodology for successful diagnosis is highlighted.
Article
Oncology
Grigoris Effraimidis, Ulrich Knigge, Maria Rossing, Peter Oturai, Ase Krogh Rasmussen, Ulla Feldt-Rasmussen
Summary: Neuroendocrine neoplasms (NENs) are rare tumors that have shown a significant increase in incidence over the past four decades. These tumors arise from neuroendocrine cells and have diverse presentations and behaviors, depending on the organ involved. Multiple endocrine neoplasia type 1 (MEN-1) is a key genetic syndrome associated with NENs and research on diagnosis and treatment is progressing.
SEMINARS IN CANCER BIOLOGY
(2022)
Review
Oncology
Nicolas Sahakian, Frederic Castinetti, Pauline Romanet
Summary: Medullary thyroid cancer (MTC) is a rare disease that can be sporadic or genetically determined. The significance of RET signaling pathways in the pathogenesis of MTC is suggested by the presence of RET pathogenic variants in aggressive forms of both sporadic and genetically determined MTC. However, the relationship between RET codon-related MTC aggressiveness is still debated, and other factors such as RET polymorphisms, epigenetic factors, environmental factors, MET alterations, and RAS family genetic alterations may also impact the progression of the disease.
Article
Surgery
F. Fanget, M. S. Demarchi, L. Maillard, A. Lintis, M. Decaussin, J. C. Lifante
Summary: This study demonstrated that patients with normalized postoperative calcitonin levels in medullary thyroid cancer had a higher risk of disease recurrence compared to those with undetectable calcitonin levels, highlighting the importance of postoperative calcitonin levels in disease prognosis.
BRITISH JOURNAL OF SURGERY
(2021)
Article
Oncology
Lamis Yehia, Charis Eng
Summary: The study of characteristics of breast cancer in young women has important implications for personalized genomics-driven management.
CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Seth J. Rotz, Naseer Sangwan, Matthew Nagy, Alice Tzeng, Margaret Jia, Maria Moncaliano, Navneet S. Majhail, Charis Eng
Summary: The intestinal microbiome diversity of long-term survivors of pediatric cancer is reduced, and radiation therapy may further decrease the diversity. The microbiome composition is associated with metabolic syndrome, obesity, and chronic inflammation in these survivors.
PEDIATRIC HEMATOLOGY AND ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jennifer E. Dawson, Iris Nira Smith, William Martin, Krishnendu Khan, Feixiong Cheng, Charis Eng
Summary: PTEN, a chief regulator of cellular processes and a major tumor suppressor gene, remains elusive in terms of its structure and regulation of protein stability, post-translational modifications, and protein-protein interactions. In this study, multiple methods were employed to investigate the structure and molecular behavior of PTEN's PBD. The findings suggest that the PBD exists in multiple conformations, highlighting the importance of understanding how these specific conformational substates contribute to PTEN function, disease pathogenesis, and modulation of its tumor suppressor activity.
Article
Genetics & Heredity
Lamis Yehia, Ying Ni, Tammy Sadler, Thomas W. Frazier, Charis Eng
Summary: A metabolomics study on PHTS individuals with ASD/DD, cancer, or both phenotypes found differentially abundant metabolites and distinct metabolic phenotypes, indicating that metabolites may enable more accurate risk predictions and prevention in individual PHTS patients at highest risk.
NPJ GENOMIC MEDICINE
(2022)
Article
Genetics & Heredity
Takae Brewer, Lamis Yehia, Peter Bazeley, Charis Eng
Summary: Findings from this study suggest that breast cancers arising from germline PTEN variants have distinct genomic characteristics compared to sporadic breast cancers, including distinct somatic mutational landscape, increased genomic instability, and higher frequency of somatic PTEN variants. These findings have important implications for the personalized management of PTEN-related breast cancers.
AMERICAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Endocrinology & Metabolism
Gilman Plitt, Takae Brewer, Lamis Yehia, Judy Jin, Joyce Shin, Charis Eng
Summary: This study investigated the time to develop thyroid nodules and thyroid cancer in PHTS patients. The findings suggest that PHTS patients without nodules on ultrasound can extend surveillance intervals to 3-5 years, while patients with clinically nonactionable nodules can extend surveillance intervals to 2-3 years, instead of the current recommendation of annual ultrasounds.
Article
Chemistry, Medicinal
Iris N. Smith, Jennifer E. Dawson, James Krieger, Stetson Thacker, Ivet Bahar, Charis Eng
Summary: The study reveals the mechanism of CTT phosphorylation dynamics in PTEN and identifies potential druggable allosteric sites in a previously believed clinically undruggable protein.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Gastroenterology & Hepatology
Lamis Yehia, Brandie Heald, Charis Eng
Summary: Hamartomatous polyposis syndromes are a group of clinically distinct disorders characterized by hamartomatous polyps in the gastrointestinal tract. These syndromes include juvenile polyposis syndrome, Peutz-Jeghers syndrome, and PTEN hamartoma tumor syndrome. Differentiating histologically between the polyps in each syndrome is challenging. Additionally, these syndromes are associated with increased risks of gene-specific and organ-specific cancers. Germline pathogenic variants can be identified and facilitate molecular diagnosis and gene-enabled management. Timely recognition enables presymptomatic cancer surveillance and management, although there are currently no standard agents for prevention.
Article
Chemistry, Physical
Iris N. Smith, Jennifer E. Dawson, Charis Eng
Summary: PTEN is a key regulator of the PI3K/AKT/mTOR signaling pathway, and its phosphorylation affects its tumor suppressor function. Mutations in PTEN are associated with PTEN hamartoma tumor syndrome and autism spectrum disorder. This study used a comparative protein structure network approach to investigate the conformational dynamics induced by PTEN phosphorylation and identified differences between PTEN-ASD and PTEN-cancer phenotypes. The findings suggest that CTT phosphorylation affects the flexibility, inter-residue contacts, and allosteric communication patterns of PTEN.
JOURNAL OF PHYSICAL CHEMISTRY B
(2023)
Editorial Material
Oncology
Lamis Yehia, Maria Laura Centomo, Pier Paolo Pandol, Charis Eng
JOURNAL OF THORACIC ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
Shyam K. Poudel, Roshan Padmanabhan, Heloni Dave, Kathryn Guinta, Tyler Stevens, Madhusudhan R. Sanaka, Prabhleen Chahal, Davendra P. S. Sohal, Alok A. Khorana, Charis Eng
Summary: This study aimed to find malignancy-related microbiomic fingerprints in bile samples from patients with pancreaticobiliary malignancies. The results showed that both benign and malignant pancreaticobiliary diseases have distinct microbiomic compositions, and the relative abundance of certain bacteria varies between different types of pancreaticobiliary malignancies.
Article
Biochemistry & Molecular Biology
Masahiro Hitomi, Juan Venegas, Shin Chung Kang, Charis Eng
Summary: Individuals with a PTEN germline mutation, known as PTEN hamartoma tumor syndrome (PHTS), exhibit a range of symptoms including hamartomas, predisposition to cancers, and autism spectrum disorder (ASD). The specific genotype-phenotype correlations of PTEN mutations are not yet well-established due to limited information on the impact of these mutations on PTEN function. To address this knowledge gap, the researchers compared the functional effects of two selected missense PTEN mutations, G132D and M134R, which are associated with distinct clinical phenotypes of ASD and thyroid cancer without ASD, respectively. The findings suggest that the ASD-associated G132D allele promotes genome instability by prematurely reentering the cell cycle with incomplete DNA repair.
Article
Genetics & Heredity
Takae Brewer, Lamis Yehia, Peter Bazeley, Charis Eng
Summary: This study revealed distinct somatic landscape features in breast cancers derived from germline PTEN variants, including unique copy number variations and transcriptomic signatures. The transcriptome data also identified a key pathway associated with tumorigenesis involving vitamin E degradation in patients with pathogenic germline PTEN variants.
NPJ GENOMIC MEDICINE
(2023)
Article
Genetics & Heredity
Ruipeng Wei, Lamis Yehia, Ying Ni, Charis Eng
Summary: Cancer and autism spectrum disorder/developmental delay (ASD/DD) are common clinical phenotypes in individuals with germ-line PTEN variants (PTEN hamartoma tumor syndrome, PHTS). This study investigates the mitochondrial genome (mtDNA) in PHTS individuals and finds that mtDNA may act as a modifier of ASD/DD versus cancer in PHTS. The study shows that PHTS-onlyASD/DD has higher mtDNA copy number than PHTS-onlyCancer group and PHTS-neither group has higher mtDNA variant burden than PHTS-ASDCancer group.
HUMAN GENETICS AND GENOMICS ADVANCES
(2023)
Article
Clinical Neurology
Robyn M. Busch, Lamis Yehia, Ingmar Bluemcke, Bo Hu, Richard Prayson, Bruce P. Hermann, Imad M. Najm, Charis Eng
Summary: Memory impairment in temporal lobe epilepsy is associated with molecular alterations within temporal lobe subregions that are independent from hippocampal cell loss, demographic variables, and disease characteristics. Each temporal subregion shows a unique molecular signature associated with memory impairment.
BRAIN COMMUNICATIONS
(2022)
Article
Genetics & Heredity
Katerina S. Kucera, Beth Lincoln Boyea, Brooke Migliore, Sarah Nelson Potter, Veronica R. Robles, Oksana Kutsa, Heidi Cope, Katherine C. Okoniewski, Anne Wheeler, Catherine W. Rehder, Edward C. Smith, Holly L. Peay
Summary: Screening for elevated CK-MM levels in dried blood spots is a feasible method to identify newborns with DMD. Including specific cutoffs, repeat testing, and genetic sequencing can improve the accuracy and sensitivity of screening.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Madeline Currey, Ilana Solomon, Sarah Mcgraw, Jenny Shen, Francisco Munoz, Ernesto Sosa, Vanessa Puello-Lozano, Sam Wing, Lisa Lopez, Michelle Afkhami, Janine Lobello, Szabolcs Szelinger, Stacy W. Gray
Summary: This study conducted qualitative interviews with cancer patients and providers to identify gaps in clinical care and propose care delivery solutions for the return of secondary germline findings. The responses of patients varied depending on the amount of pre-test counseling they received, and providers identified insufficient clinic time as a major barrier to pretest education. Online support tools and standardized pre-test education models were favored by providers. There were differing perspectives on how pre-test education should be integrated into clinical workflows, but agreement on the inclusion of differences between somatic and germline testing, likelihood of medically actionable findings, and the possibility of being referred to a genetics provider.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Kiely N. James, Shimul Chowdhury, Yan Ding, Sergey Batalov, Kelly Watkins, Yong Hyun Kwon, Lucitia Van Der Kraan, Katarzyna Ellsworth, Stephen F. Kingsmore, Lucia Guidugli
Summary: This study used genome sequencing to detect a wide range of copy-number variants (CNVs) and other non-single nucleotide variant/indel variant types. These genetic alterations accounted for 15.8% of reported variants, with deletions being the most common type. The study also found that additional genetic tests were ordered in some cases, but failed to report the variants detected by genome sequencing.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Asem Berkalieva, Nicole R. Kelly, Ashley Fisher, Samuel F. Hohmann, Monisha Sebastin, Miranda Di Biase, Katherine E. Bonini, Priya Marathe, Jacqueline A. Odgis, Sabrina A. Suckiel, Michelle A. Ramos, Rosamond Rhodes, Noura S. Abul-Husn, John M. Greally, Carol R. Horowitz, Melissa P. Wasserstein, Eimear E. Kenny, Bruce D. Gelb, Bart S. Ferket
Summary: The study aims to understand the effects of returning diagnostic sequencing results on clinical actions and economic outcomes for pediatric patients with suspected genetic disorders. The results showed that patients with positive findings were more likely to receive specialist consultation, but there were no significant increases in overall physician services and costs. More large-scale studies are needed to confirm these findings.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Kirstine Stochholm, Camilla Holmgard, Shanlee M. Davis, Claus H. Gravholt, Agnethe Berglund
Summary: This study assessed the incidence, prevalence, and age at diagnosis of individuals with 45,X/46,XY mosaicism and described the associated mortality pattern. The study found an increasing incidence of 45,X/46,XY mosaicism in males and a stable incidence in females. Males were diagnosed at an older age than females. Additionally, 45,X/46,XY mosaicism was associated with increased all-cause mortality.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Yunjia Chen, Ender Karaca, Nathaniel H. Robin, Dana Goodloe, Ali Al-Beshri, S. Joy Dean, Anna C. E. Hurst, Andrew J. Carroll, Fady M. Mikhail
Summary: This study confirms the association between DLG2 intragenic deletions and neurodevelopmental disorders, supports the haploinsufficiency of the DLG2 gene, and suggests a potential association between these deletions and congenital anomalies and dysmorphism.
GENETICS IN MEDICINE
(2024)
