Article
Public, Environmental & Occupational Health
Gemme Campbell-Salome, Adam H. Buchanan, Miranda L. G. Hallquist, Alanna K. Rahm, Heather Rocha, Amy C. Sturm
Summary: Individuals with Lynch syndrome face healthcare barriers in managing uncertainty, leading to increased uncertainty and anxiety. To reduce uncertainty, they use alternative strategies such as advocating for themselves with providers, seeking information online, and communicating with family for emotional support.
PATIENT EDUCATION AND COUNSELING
(2021)
Article
Multidisciplinary Sciences
Abdul Khalid Siraj, Rong Bu, Tariq Masoodi, Sandeep Kumar Parvathareddy, Kaleem Iqbal, Wael Al-Haqawi, Hassan Al-Dossari, Saud Azam, Zeeshan Qadri, Padmanaban Annaiyappanaidu, Fouad Al-Dayel, Khawla Sami Al-Kuraya
Summary: RNF43 mutations are frequently found in Middle Eastern CRC, with a strong association with right-sided and sporadic MSI CRC, and no association with other clinical and pathological features.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Ayushi Jain, Maryam Alimirah, Heather Hampel, Rachel Pearlman, Jianing Ma, Jing Peng, Matthew F. Kalady, Peter P. Stanich
Summary: Multiple colorectal adenomas (MCRA) are not uncommon in Lynch syndrome and are associated with a significantly increased likelihood of advanced colon neoplasia.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Yiming Li, Lulu Yu, Jiajia Cui, Jiye Yin, Wei Wu
Summary: This is a report on a multi-generational Chinese family with LS. Through MSI testing, IHC, and WES, a splicing variant in the MSH2 gene was identified as the cause of LS. This study highlights the importance of LS gene testing.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Karolin Bucksch, Silke Zachariae, Aysel Ahadova, Stefan Aretz, Reinhard Buttner, Heike Goergens, Elke Holinski-Feder, Robert Hueneburg, Matthias Kloor, Magnus Knebel Doeberitz, Swetlana Ladigan-Badura, Gabriela Moeslein, Monika Morak, Jacob Nattermann, Huu Phuc Nguyen, Claudia Perne, Silke Redler, Ariane Schmetz, Verena Steinke-Lange, Harald Surowy, Deepak B. Vangala, Juergen Weitz, Markus Loeffler, Christoph Engel
Summary: This study aimed to characterize and compare the risks for adenoma and CRC in Lynch syndrome (LS), Lynch-like syndrome (LLS) and familial colorectal cancer type X (FCCX). The study found similar risks for colorectal adenomas, but different risks for first and metachronous CRC between the three risk groups, with CRC risk highest in LS, followed by LLS and lowest in FCCX. Male sex and a prevalent adenoma in the index colonoscopy were associated with a higher risk for incident adenoma and CRC.
INTERNATIONAL JOURNAL OF CANCER
(2022)
Article
Oncology
Shumin Jia, Xiaodan Wu, Yiheng Zhang, Meifen Zhang
Summary: The study showed that Chinese Lynch syndrome-associated colorectal cancer patients had high adherence to surveillance for colorectal cancer, but lower adherence for extracolorectal cancers. Adherence to surveillance was associated with patients' age and occupation. Chinese patients had slightly higher self-concept scores compared to foreign patients.
EUROPEAN JOURNAL OF CANCER CARE
(2021)
Article
Oncology
Daniele Fanale, Lidia Rita Corsini, Chiara Brando, Alessandra Dimino, Clarissa Filorizzo, Luigi Magrin, Roberta Sciacchitano, Alessia Fiorino, Tancredi Didier Bazan Russo, Valentina Calo, Juan Lucio Iovanna, Edoardo Francini, Antonio Russo, Viviana Bazan
Summary: Lynch syndrome is a genetic condition associated with an increased predisposition to colorectal cancer and other tumors. The most efficient strategy to identify patients with this syndrome is still unclear. A study found that analyzing tissue microsatellite instability according to the revised Bethesda guidelines is the best selection approach, but using different selection methods as complementary strategies helps reduce underdiagnosis.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Alejandro Martinez-Roca, Mar Giner-Calabuig, Oscar Murcia, Adela Castillejo, Jose Luis Soto, Anabel Garcia-Heredia, Rodrigo Jover
Summary: Lynch-like syndrome refers to cases of colorectal cancer where epigenetics and genetic mutations play a significant role in its development. This syndrome presents a mixture of characteristics between hereditary and sporadic cases, making it challenging to determine the exact genetic abnormalities involved.
Article
Gastroenterology & Hepatology
Jordan J. Karlitz, Amanda Phillips, Kelly S. Sorrells, Shanti Rao
Summary: This study is the first to assess hereditary CRC in a large US regional founder population. While no clear Cajun founder pathogenic variants were identified in the results, larger studies are warranted, which could also help clarify the clinical significance of the adenomatous polyposis coli variant of unknown significance.
CLINICAL AND TRANSLATIONAL GASTROENTEROLOGY
(2021)
Article
Oncology
Adam Solomon, Zoya Alteber, David Bassan, Adi Sharbi-Yunger, Simon Esbit, Esther Tzehoval, Lea Eisenbach
Summary: Lynch Syndrome is an autosomal dominant genetic condition that causes a high risk of colorectal cancer. A study using a mouse model found a novel tumor neo-antigen and demonstrated the effectiveness of an immune vaccine, which may have a protective effect for patients carrying LS mutations.
INTERNATIONAL JOURNAL OF CANCER
(2022)
Review
Endocrinology & Metabolism
Marta Domenech, Elia Grau, Ares Solanes, Angel Izquierdo, Jesus Del Valle, Cristina Carrato, Marta Pineda, Nuria Duenas, Magda Pujol, Conxi Lazaro, Gabriel Capella, Joan Brunet, Matilde Navarro
Summary: LS is the most common inherited colorectal and endometrial cancer syndrome caused by germline mutations in DNA mismatch repair genes. In a Spanish LS cohort, the prevalence of ACC was 0.47%, mainly associated with MSH2 gene mutations. MMR protein immunohistochemistry screening could be an efficient strategy to detect LS in patients with ACC.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2021)
Article
Oncology
Soyoun Rachel Kim, Alicia Tone, Raymond H. Kim, Matthew Cesari, Blaise A. Clarke, Lua Eiriksson, Tae L. Hart, Melyssa Aronson, Spring Holter, Alice Lytwyn, Manjula Maganti, Leslie Oldfield, Steven Gallinger, Marcus Q. Bernardini, Amit M. Oza, Bojana Djordjevic, Jordan Lerner-Ellis, Emily van de Laar, Danielle Vicus, Trevor J. Pugh, Aaron Pollett, Sarah E. Ferguson
Summary: The implementation of a navigated genetic program resulted in a high rate of genetic assessment in patients with endometrial or nonserous/nonmucinous ovarian cancer at risk for Lynch syndrome.
Review
Oncology
Pandu P. Nugroho, Siti Alyaa S. Ghozali, Daniel D. Buchanan, Mia Pisano, Jeanette C. Reece
Summary: This study systematically reviewed the cancer risks in Lynch-like syndrome (LLS) patients and their relatives. The findings showed an increased risk of colorectal cancer (CRC) in LLS patients and relatives, while the risk of endometrial cancer was relatively lower. Therefore, increased colonoscopy surveillance strategies are recommended for LLS patients and relatives, and extended screening intervals may be advised for low-risk families. Further research is needed to resolve the molecular characterization and definition of LLS in order to better understand the associated cancer risks.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Vitaly Shubin, Yury Shelygin, Sergey Achkasov, Oleg Sushkov, Ilya Nazarov, Alexey Ponomarenko, Iuliia Alimova, Anna Loginova, Aleksey Tsukanov
Summary: The aim of this study was to determine the characteristics of Russian patients with microsatellite instability (MSI) tumors. The results showed that patients with MSI tumors differed in the age of diagnosis, tumor localization, time of cancer recurrence, and stage of the disease. Patients whose tumors had MSI status had higher overall and disease-free survival rates.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Oncology
Antonio Nolano, Alessia Medugno, Silvia Trombetti, Raffaella Liccardo, Marina De Rosa, Paola Izzo, Francesca Duraturo
Summary: Lynch syndrome is a common form of hereditary colorectal cancer associated with variants in Mismatch Repair (MMR) genes. However, many variants identified in these genes remain of uncertain significance. Therefore, individuals with a clinical suspicion of LS often receive a diagnosis of Lynch-like syndrome. This review summarizes the main aspects of Lynch syndrome, recent advances in molecular diagnosis, and the factors that determine the loss of expression of MMR genes.
Article
Psychiatry
Andrea Vergallo, Simone Lista, Yuhai Zhao, Pablo Lemercier, Stefan J. Teipel, Marie-Claude Potier, Marie-Odile Habert, Bruno Dubois, Walter J. Lukiw, Harald Hampel
Summary: The study identified brain-enriched miRNAs in a cohort of cognitively normal individuals with subjective memory complaints. It investigated the impact of age, sex, and the APOE epsilon 4 allele on miRNA plasma concentrations and explored associations with brain metabolic uptake using PET imaging. The results suggest potential associations between miRNA concentrations and neuroimaging biomarkers of AD pathophysiology.
TRANSLATIONAL PSYCHIATRY
(2021)
Article
Clinical Neurology
Andrea Vergallo, Pablo Lemercier, Enrica Cavedo, Simone Lista, Eugeen Vanmechelen, Ann De Vos, Henrik Zetterberg, Kaj Blennow, Marie-Odile Habert, Marie-Claude Potier, Bruno Dubois, Stefan Teipel, Harald Hampel
Summary: The study identified a positive correlation between plasma BACE1 protein concentrations and AD biomarkers of neurodegeneration, suggesting a potential role of BACE1 in Alzheimer's disease progression.
ALZHEIMERS & DEMENTIA
(2021)
Article
Biochemistry & Molecular Biology
Rosie O'Shea, Nicole M. Rankin, Maira Kentwell, Margaret Gleeson, Katherine M. Tucker, Heather Hampel, Natalie Taylor, Sarah Lewis
Summary: Mainstream genetic testing in routine oncology care requires implementation research to inform intervention design. An online survey in Australia found that most healthcare professionals agreed that aligning genetic testing with universal tumor screening could streamline care for patients. Additionally, there were disagreements among healthcare professional groups about knowledge and self-efficacy in using genetic test results for treatment management decisions. The findings from implementation research can guide targeted interventions and a model for genetic testing integration into oncology care.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2021)
Review
Cell Biology
Harald Hampel, Robert Nistico, Nicholas T. Seyfried, Allan I. Levey, Erica Modeste, Pablo Lemercier, Filippo Baldacci, Nicola Toschi, Francesco Garaci, George Perry, Enzo Emanuele, Pedro L. Valenzuela, Alejandro Lucia, Andrea Urbani, Giulia M. Sancesario, Mark Mapstone, Massimo Corbo, Andrea Vergallo, Simone Lista
Summary: Alzheimer's disease is characterized by complex pathophysiology with high heterogeneity, requiring a holistic approach to fully capture its multifaceted nature. Integrating omics sciences and systems biology network approaches can help detect and describe the biological changes occurring in the progression of AD.
AGEING RESEARCH REVIEWS
(2021)
Review
Clinical Neurology
Harald Hampel, Leslie M. Shaw, Paul Aisen, Christopher Chen, Alberto Lleo, Takeshi Iwatsubo, Atsushi Iwata, Masahito Yamada, Takeshi Ikeuchi, Jianping Jia, Huali Wang, Charlotte E. Teunissen, Elaine Peskind, Kaj Blennow, Jeffrey Cummings, Andrea Vergallo
Summary: The article discusses the necessity and inconsistency of lumbar puncture in the diagnosis of Alzheimer's disease, highlighting the importance of lumbar puncture in early diagnosis and treatment.
ALZHEIMERS & DEMENTIA
(2022)
Article
Clinical Neurology
Harald Hampel, Andrea Vergallo, Takeshi Iwatsubo, Min Cho, Kiyoshi Kurokawa, Huali Wang, H. Ricky Kurzman, Christopher Chen
Summary: With population growth and aging, the number of people with dementia and related disorders will increase significantly, posing significant challenges to society, healthcare, and the economy. Most countries are taking early actions to mitigate the disease burden, including a specific focus on early action in national dementia strategies, implementing public health initiatives for risk reduction and early detection and diagnosis, supporting research for early detection and risk reduction, and enacting a system for early brain health screening.
ALZHEIMERS & DEMENTIA
(2022)
Review
Oncology
Heather Hampel, Matthew B. Yurgelun
Summary: The use of germline genetic testing is increasing among cancer patients due to the availability of multigene panel tests, decreased costs, and improved insurance coverage. The US Food and Drug Administration's approval of genotype-directed therapies also contributes to this trend. Additionally, the National Comprehensive Cancer Network has endorsed germline genetic testing for certain cancer types. This article debates the advantages and disadvantages of offering germline multigene panel testing to all patients diagnosed with any GI cancer.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Alessandro Galgani, Andrea Vergallo, Nicole Campese, Francesco Lombardo, Nicola Pavese, Lucia Petrozzi, Annalisa LoGerfo, Maria Franzini, Denise Cecchetti, Stefano Puglisi-Allegra, Carla L. Busceti, Gabriele Siciliano, Gloria Tognoni, Filippo Baldacci, Simone Lista, Harald Hampel, Francesco Fornai, Filippo S. Giorgi
Summary: Translational and clinical research has shown that neuroinflammation plays a critical role in the pathophysiology of Alzheimer's disease (AD). Blood-based biomarkers, such as cytokines and interleukins, have been studied as indicators of neuroinflammation in AD. However, inconsistent results have been reported due to lack of standardization. This study used machine-learning and statistical analysis to explore the impact of age, sex, and APOE genotype on cytokines. The results showed sex differences in IL12 and an APOE-related difference in IL10, with IL1 beta being significantly associated with MCI-to-dementia conversion. Further clinical research is needed to understand the role of plasma cytokines in neuroimmune and inflammatory dynamics in AD.
JOURNAL OF NEUROCHEMISTRY
(2022)
Article
Clinical Neurology
Harald Hampel, Aya Elhage, Jeffrey Cummings, Kaj Blennow, Peng Gao, Clifford R. Jack, Andrea Vergallo
NEURODEGENERATIVE DISEASE MANAGEMENT
(2022)
Article
Clinical Neurology
Harald Hampel, Aya Elhage, Leslie M. Shaw, Paul Aisen, Christopher Chen, Alberto Lleo, Takeshi Iwatsubo, Atsushi Iwata, Masahito Yamada, Takeshi Ikeuchi, Jianping Jia, Huali Wang, Charlotte E. Teunissen, Elaine Peskind, Kaj Blennow, Jeffrey Cummings, Andrea Vergallo
Summary: This article is a summary of the safe use of lumbar puncture in diagnosing Alzheimer's disease and other forms of dementia. Despite the low risk of complications, there may be reluctance among physicians and patients to recommend or undergo this procedure. Patient education, specialist training, and new methods for patient safety are important factors in supporting the widespread use of lumbar puncture in Alzheimer's disease.
NEURODEGENERATIVE DISEASE MANAGEMENT
(2022)
Article
Oncology
Leigha Senter, Deloris Veney, Taylor Surplus, Marcy Haynam, Elizabeth J. Adams, Heather Hampel, Amanda E. Toland, Carolyn J. Presley, Tasleem J. Padamsee, Clara N. Lee, Shelly R. Hovick, Daniel G. Stover
Summary: Tumor genomic testing (TGT) is an important part of cancer care, but many patients have limited understanding of genomics and are not informed about potential incidental germline findings. A PDSA approach is being used to assess and improve patient education before TGT, including reviewing guidelines, conducting focus groups and interviews, and creating a patient-directed animated video.
JCO ONCOLOGY PRACTICE
(2023)
Review
Neurosciences
Harald Hampel, Peng Gao, Jeffrey Cummings, Nicola Toschi, Paul M. Thompson, Yan Hu, Min Cho, Andrea Vergallo
Summary: Neurological and psychiatric diseases are highly genetically and patho-physiologically heterogeneous. Precision medicine (PM) offers an alternative approach to traditional medical paradigms, focusing on the underlying biology of diseases. This article proposes a PM architecture for central nervous system diseases, based on multimodal biomarkers, systems medicine, digital health technologies, and data science. Alzheimer's disease is discussed as an example, showcasing its potential for PM-oriented neuroscience drug development and advanced healthcare practice.
TRENDS IN NEUROSCIENCES
(2023)
Article
Clinical Neurology
Harald Hampel, Yan Hu, John Hardy, Kaj Blennow, Christopher Chen, George Perry, Seung Hyun Kim, Victor L. Villemagne, Paul Aisen, Michele Vendruscolo, Takeshi Iwatsubo, Colin L. Masters, Min Cho, Lars Lannfelt, Jeffrey L. Cummings, Andrea Vergallo
Summary: This summary reviews the evidence supporting the role of the amyloid-b (Ab) pathway in Alzheimer's disease (AD) and emphasizes the importance of targeting this pathway in early stages of the disease. Understanding and targeting the A beta pathway can lead to better therapeutic outcomes and management of AD.
NEURODEGENERATIVE DISEASE MANAGEMENT
(2023)
Article
Cell Biology
Harald Hampel, Rhoda Au, Soeren Mattke, Wiesje M. M. van der Flier, Paul Aisen, Liana Apostolova, Christopher Chen, Min Cho, Susan De Santi, Peng Gao, Atsushi Iwata, Ricky Kurzman, Andrew J. J. Saykin, Stefan Teipel, Bruno Vellas, Andrea Vergallo, Huali Wang, Jeffrey Cummings
Summary: This Perspective discusses the reconceptualization of Alzheimer's disease as a clinical and biological construct and proposes a new framework for clinical care pathways that incorporates biomarker-guided and digitally facilitated decision-making algorithms. The challenges and potential solutions for this transformation are addressed.
Article
Oncology
Monica D. Levine, Rachel Pearlman, Heather Hampel, Casey Cosgrove, David Cohn, Alexis Chassen, Adrian Suarez, David A. Barrington, Joseph P. McElroy, Steven Waggoner, John Nakayama, Caroline Billingsley, Kim Resnick, Stephen Andrews, Sareena Singh, Eric Jenison, Aine Clements, Robert Neff, Paul J. Goodfellow
Summary: This prospective multicenter study revealed actionable germline variants in 10% of unselected women with newly diagnosed EC, supporting the use of up-front MGPT for all EC patients. The discovery that BRCA1 or BRCA2 heterozygotes frequently had type II cancers points to therapeutic opportunities for women with aggressive histologic EC subtypes.
JCO PRECISION ONCOLOGY
(2021)
