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
Pathology
Shaymaa Hegazy, Randall E. Brand, Beth Dudley, Eve Karloski, Jamie L. Lesnock, Esther Elishaev, Reetesh K. Pai
Summary: MMR-deficient benign endometrial glands can be detected in LS patients, and their presence may serve as a biomarker for increased risk of endometrial carcinoma development in LS.
AMERICAN JOURNAL OF SURGICAL PATHOLOGY
(2023)
Article
Cell Biology
Jinru Shia
Summary: Microsatellite instability (MSI) is recognized as a diverse molecular phenotype in human neoplasms, with variations in genotype and phenotype within and across tumor types. Advances in understanding this diversity have been made, but its potential impact on the effective use of current MSI detection tools is significant.
Review
Gastroenterology & Hepatology
Guillaume Perrod, Gabriel Rahmi, Christophe Cellier
Summary: Lynch syndrome is a hereditary predisposition to colorectal cancer, and regular colonoscopies with high definition screening can reduce the incidence and mortality of colorectal cancer, recommended to start at the age of 20-25.
DIGESTIVE ENDOSCOPY
(2021)
Article
Oncology
Tomoyuki Ono, Tatsuro Yamaguchi, Misato Takao, Ekumi Kojika, Takeru Iijima, Shin-ichiro Horiguchi
Summary: This study found that F. nucleatum load was higher in MSI CRC patients. There was no significant difference in the association between F. nucleatum load and clinicopathological characteristics in hereditary and sporadic MSI CRC. These findings may have implications for preventing CRC in hereditary MSI CRC.
INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Oncology
Meihua Ye, Guoqing Ru, Hang Yuan, Lili Qian, Xianglei He, Shuangshuang Li
Summary: This study retrospectively collected data from 502 CRC patients and found that MSI-H is common in CRC, and IHC has high accuracy in detecting MSI. In addition, the study identified some clinicopathological characteristics associated with MSI-H and recommended the development of testing packages of different sizes in clinical practice for comprehensive selection.
FRONTIERS IN ONCOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Martina Lepore Signorile, Vittoria Disciglio, Gabriella Di Carlo, Antonio Pisani, Cristiano Simone, Giuseppe Ingravallo
Summary: This article introduces different molecular models of colorectal carcinogenesis in Lynch syndrome patients and explains three different pathways: developing adenomas in an MMR-proficient background, early MMR deficiency before adenoma formation on histologically normal gut surface, and skipping the adenoma step with rapid invasive tumor growth in an MMR-deficient context.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Swetlana Ladigan-Badura, Deepak B. Vangala, Christoph Engel, Karolin Bucksch, Robert Hueneburg, Claudia Perne, Jacob Nattermann, Verena Steinke-Lange, Nils Rahner, Hans K. Schackert, Juergen Weitz, Matthias Kloor, Judith Kuhlkamp, Huu Phuc Nguyen, Gabriela Moeslein, Christian Strassburg, Monika Morak, Elke Holinski-Feder, Reinhard Buettner, Stefan Aretz, Markus Loeffler, Wolff Schmiegel, Christian Pox, Karsten Schulmann
Summary: Regular upper GI endoscopy surveillance for LS patients starting from the age of 30 can successfully detect gastric cancer in early stages, leading to more frequent diagnoses in early-stage disease compared to symptomatic diagnoses. The study emphasizes the importance of early detection through regular screenings.
INTERNATIONAL JOURNAL OF CANCER
(2021)
Article
Gastroenterology & Hepatology
Laura Monje-Garcia, Timothy Bill, Lindsay Farthing, Nate Hill, Emma Kipps, Angela F. F. Brady, Zoe Kemp, Katie Snape, Alistair Myers, Muti Abulafi, Kevin Monahan
Summary: This study aimed to measure geographic variation in Lynch syndrome (LS) testing among colorectal cancer (CRC) patients within the RM Partners West London cancer alliance and deliver an effective diagnostic pathway. The LS pathway audit revealed that improvement recommendations have been implemented, resulting in significant improvements in the percentage of patients undergoing tumor marker testing (p=0.008), further testing (p=0.03), and referral for genetic testing (p=0.02).
COLORECTAL DISEASE
(2023)
Article
Oncology
Raffaella Liccardo, Raffaele Sessa, Silvia Trombetti, Marina De Rosa, Paola Izzo, Michela Grosso, Francesca Duraturo
Summary: The dysregulation of MMR genes, especially MSH2, plays a crucial role in the pathogenesis of Lynch Syndrome, a hereditary colorectal cancer. MiRNA miR-137 has been identified to regulate MSH2 expression via its 3'UTR region, suggesting a potential mechanism for tumorigenesis in colon cells.
Article
Oncology
Alice Talbot, Emily O'Donovan, Eileen Berkley, Carmel Nolan, Roisin Clarke, David Gallagher
Summary: Lynch syndrome (LS) is responsible for 2-4% of hereditary colorectal cancers and is characterized by mismatch repair protein deficiency. A retrospective review in Ireland found that LS patients most commonly had colorectal cancer, followed by breast and endometrial cancer. The study also identified significant differences in cancer type based on the specific gene involved in LS.
Article
Oncology
Wen-Long Guan, Yue Ma, Yue-Hong Cui, Tian-Shu Liu, Yan-Qiao Zhang, Zhi-Wei Zhou, Jian-Ying Xu, Li-Qiong Yang, Jia-Yu Li, Yu-Ting Sun, Rui-Hua Xu, Feng-Hua Wang, Miao-Zhen Qiu
Summary: This study aimed to analyze the relationship between dMMR/MSI-H and clinicopathological features along with survival in GC patients. The results showed that dMMR/MSI-H patients have specific clinicopathological characteristics and better prognosis compared to pMMR patients.
FRONTIERS IN ONCOLOGY
(2021)
Review
Immunology
Vladimir Roudko, Cansu Cimen Bozkus, Benjamin Greenbaum, Aimee Lucas, Robert Samstein, Nina Bhardwaj
Summary: Defective DNA mismatch repair is associated with various cancer types, including Lynch syndrome which increases the risk of malignancy. MSI-H tumors can be treated with checkpoint inhibitors, but the response rates are not high.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Courtney J. Riedinger, Ashwini Esnakula, Paulina J. Haight, Adrian A. Suarez, Wei Chen, Jessica Gillespie, Alyssa Villacres, Alexis Chassen, David E. Cohn, Paul J. Goodfellow, Casey M. Cosgrove
Summary: This study aims to evaluate the therapeutic implications of mismatch-repair (MMR)/microsatellite instability (MSI) status in endometrial cancer (EC). The results show that subclonal/heterogeneous MMR expression is associated with a high recurrence rate and MMR deficiency in metastatic/recurrent sites.
Article
Multidisciplinary Sciences
Chul Seung Lee, In Hye Song, Ahwon Lee, Jun Kang, Yoon Suk Lee, In Kyu Lee, Young Soo Song, Sung Hak Lee
Summary: Targeted NGS technology can detect specific mutations in CRC patients, with TP53 and ATM mutations showing significant associations with clinicopathological characteristics and survival outcomes.
SCIENTIFIC REPORTS
(2021)
Article
Medicine, General & Internal
Josep M. Llovet, Robin Kate Kelley, Augusto Villanueva, Amit G. Singal, Eli Pikarsky, Sasan Roayaie, Riccardo Lencioni, Kazuhiko Koike, Jessica Zucman-Rossi, Richard S. Finn
Summary: Liver cancer, particularly hepatocellular carcinoma (HCC), poses a significant global health challenge with rising incidence projected to exceed 1 million cases by 2025. Infection by hepatitis B and C viruses remains a major risk factor for HCC, while non-alcoholic steatohepatitis is emerging as a more common risk factor in Western countries. Advances in systemic therapies for HCC, including immunotherapies and targeted therapies, are expected to revolutionize the management of this disease.
NATURE REVIEWS DISEASE PRIMERS
(2021)
Article
Gastroenterology & Hepatology
Dror Kolodkin-Gal, Lior Roitman, Yossi Ovadya, Narmen Azazmeh, Benjamin Assouline, Yehuda Schlesinger, Rachel Kalifa, Shaul Horwitz, Yonatan Khalatnik, Anna Hochner-Ger, Ashraf Imam, Jonathan Abraham Demma, Eitan Winter, Hadar Benyamini, Sharona Elgavish, Areej A. S. Khatib, Karen Meir, Karine Atlan, Eli Pikarsky, Oren Parnas, Yuval Dor, Gideon Zamir, Ittai Ben-Porath, Valery Krizhanovsky
Summary: Cellular senescence limits tumourigenesis by blocking cell proliferation, but senescent cells can also promote tumour growth through paracrine effects. Senescent cells in early pancreatic lesions express a proinflammatory signature, and targeting these cells with the senolytic drug ABT-737 can reduce PanIN development and progression to pancreatic ductal adenocarcinoma. These findings suggest that eliminating senescent cells may be an effective preventive therapy for precancerous lesions.
Article
Genetics & Heredity
Melyssa Aronson, Chrystelle Colas, Andrew Shuen, Heather Hampel, William D. Foulkes, Hagit Baris Feldman, Yael Goldberg, Martine Muleris, Kami Wolfe Schneider, Rose B. McGee, Kory Jasperson, Arun Rangaswami, Laurence Brugieres, Uri Tabori
Summary: CMMRD is the most aggressive cancer predisposition syndrome associated with multiorgan cancers, often presenting in childhood. A multidisciplinary international working group established seven diagnostic criteria for the diagnosis of CMMRD, including definitive and likely diagnostic criteria. The criteria incorporate genetic testing, ancillary tests, and clinical manifestations to determine a diagnosis, with a focus on appropriate surveillance and treatment for improved survival.
JOURNAL OF MEDICAL GENETICS
(2022)
Article
Chemistry, Multidisciplinary
Pu Zhang, Yu Ouyang, Yang Sung Sohn, Rachel Nechushtai, Eli Pikarsky, Chunhai Fan, Itamar Willner
Summary: The study presents the synthesis of stimuli-responsive hybrid structures composed of drug-loaded UiO-66 metal-organic framework nanoparticles, NMOFs, locked by DNA tetrahedra gates. These hybrid systems combine high drug loading capacity of NMOFs and effective cell permeation properties of DNA tetrahedra, releasing drugs under different stimuli.
Article
Oncology
I Kedar, L. Walsh, G. Reznick Levi, S. Lieberman, A. Abu Shtaya, S. Naftaly Nathan, I Lagovsky, R. Tomashov-Matar, M. Goldenberg, L. Basel-Salmon, L. Katz, O. Aleme, T. Yablonski Peretz, A. Hubert, D. Rothstein, S. Castellvi-Bel, T. Walsh, M. C. King, C. C. Pritchard, Z. Levi, E. Half, I Laish, Y. Goldberg
Summary: The report identifies a novel founder deletion in Lynch syndrome in Ethiopian Jews that is associated with early-onset colorectal cancer and liposarcoma, highlighting the importance of awareness for improved patient diagnosis, surveillance, and genetic counseling. Among carriers, age at first tumor diagnosis varied, with older generations diagnosed later in life compared to younger generations.
Article
Oncology
Carol Durno, Ayse Bahar Ercan, Vanessa Bianchi, Melissa Edwards, Melyssa Aronson, Melissa Galati, Eshetu G. Atenafu, Gadi Abebe-Campino, Abeer Al-Battashi, Musa Alharbi, Vahid Fallah Azad, Hagit N. Baris, Donald Basel, Raymond Bedgood, Anne Bendel, Shay Ben-Shachar, Deborah T. Blumenthal, Maude Blundell, Miriam Bornhorst, Annika Bronsema, Elizabeth Cairney, Sara Rhode, Shani Caspi, Aghiad Chamdin, Stefano Chiaravalli, Shlomi Constantini, Bruce Crooks, Anirban Das, Rina Dvir, Roula Farah, William D. Foulkes, Zehavit Frenkel, Bailey Gallinger, Sharon Gardner, David Gass, Mithra Ghalibafian, Catherine Gilpin, Yael Goldberg, Catherine Goudie, Syed Ahmer Hamid, Heather Hampel, Jordan R. Hansford, Craig Harlos, Nobuko Hijiya, Saunders Hsu, Junne Kamihara, Rejin Kebudi, Jeffrey Knipstein, Carl Koschmann, Christian Kratz, Valerie Larouche, Alvaro Lassaletta, Scott Lindhorst, Simon C. Ling, Michael P. Link, Rebecca Loret De Mola, Rebecca Luiten, Michal Lurye, Jamie L. Maciaszek, Vanan MagimairajanIssai, Ossama M. Maher, Maura Massimino, Rose B. McGee, Naureen Mushtaq, Gary Mason, Monica Newmark, Garth Nicholas, Kim E. Nichols, Theodore Nicolaides, Enrico Opocher, Michael Osborn, Benjamin Oshrine, Rachel Pearlman, Daniel Pettee, Jan Rapp, Mohsin Rashid, Alyssa Reddy, Lara Reichman, Marc Remke, Gabriel Robbins, Sumita Roy, Magnus Sabel, David Samuel, Isabelle Scheers, Kami Wolfe Schneider, Santanu Sen, Duncan Stearns, David Sumerauer, Carol Swallow, Leslie Taylor, Gregory Thomas, Helen Toledano, Patrick Tomboc, An Van Damme, Ira Winer, Michal Yalon, Lee Yi Yen, Michal Zapotocky, Shayna Zelcer, David S. Ziegler, Stefanie Zimmermann, Cynthia Hawkins, David Malkin, Eric Bouffet, Anita Villani, Uri Tabori
Summary: Surveillance and early cancer detection are associated with improved overall survival (OS) for individuals with CMMRD. In patients undergoing surveillance, GI and other solid tumors, as well as 75% of brain cancers, were detected asymptomatically. Adherence to the surveillance protocol resulted in significantly better survival outcomes, with a 4-year OS of 79% for patients undergoing full surveillance.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Article
Genetics & Heredity
Adi Wilf-Yarkoni, Oded Shor, Avi Fellner, Mark Andrew Hellmann, Elon Pras, Hagit Yonath, Shiri Shkedi-Rafid, Lina Basel-Salmon, Lili Bazak, Ruth Eliahou, Lior Greenbaum, Hadas Stiebel-Kalish, Felix Benninger, Yael Goldberg
Summary: This study describes a common WFS1 gene variant in Ashkenazi Jews that leads to a milder disease phenotype. It was found that the disease onset caused by this variant is later in age but with relatively mild symptoms, correlated with the impact on protein thermodynamics.
NEUROLOGY-GENETICS
(2021)
Article
Oncology
Ido Laish, Eitan Friedman, Gili Levi-Reznick, Inbal Kedar, Lior Katz, Zohar Levi, Naama Halpern, Shani Parnasa, Aasem Abu-Shatya, Elizabeth Half, Yael Goldberg
Summary: This study identified 11 carriers from four seemingly unrelated Ashkenazi Jewish families who had pathogenic variants in both BRCA1/2 and DNA MMR genes. 73% of the double carriers had cancer, with a range of tumor types and ages at diagnosis. The findings suggest that the phenotype of double carriers is not associated with early disease onset or a more severe phenotype, which may have implications for genetic testing and treatment strategies.
BREAST CANCER RESEARCH AND TREATMENT
(2021)
Review
Cell Biology
Avanthika Venkatachalam, Eli Pikarsky, Yinon Ben-Neriah
Summary: Somatic mutations, traditionally linked to cancer, have been found to also occur in nontransformed cells early in life. Some of these mutations, typically associated with driving cancer, can spread widely among noncancerous tissue cells, particularly intensifying with age or exposure to external stressors. In certain states, these classic driver mutations in normal cells may play beneficial roles in maintaining homeostasis during stress and tissue repair in aging cells.
TRENDS IN CELL BIOLOGY
(2022)
Review
Oncology
Josep M. Llovet, Florian Castet, Mathias Heikenwalder, Mala K. Maini, Vincenzo Mazzaferro, David J. Pinato, Eli Pikarsky, Andrew X. Zhu, Richard S. Finn
Summary: Liver cancer, specifically hepatocellular carcinoma (HCC), is the second leading cause of cancer-related death globally. Traditional treatments involve specific drugs, but the emergence of immune checkpoint inhibitors has revolutionized the management of HCC.
NATURE REVIEWS CLINICAL ONCOLOGY
(2022)
Review
Oncology
Diana Haimov, Sari Lieberman, Sergi Castellvi-Bel, Maartje Nielsen, Yael Goldberg
Summary: Familiarity with nonmalignant features and comorbidities of cancer predisposition syndromes is important for clinicians to diagnose and interpret molecular test results. Genetic predisposition to colorectal cancer should be suspected in young patients, patients with significant family histories, multiple polyps, mismatch repair-deficient tumors, and in association with malignant or nonmalignant comorbidities. This knowledge can raise awareness, enable diagnosis, and assist in the process of genetic testing.
Article
Cell Biology
Batel Shalom, Marganit Farago, Yaser Salaymeh, Shulamit Sebban, Eli Pikarsky, Shulamit Katzav
Summary: Vav1 is normally expressed in the hematopoietic system and its mutations and overexpression are associated with malignancies. This study shows that Vav1 expression in epithelial tissues can lead to the development of B-cell lymphomas. The cross-talk between epithelial cells secreting CSF-1 and lymphocytes expressing CSF-1R may contribute to the generation of these lymphomas.
Article
Oncology
Johnathan Arnon, Michael Tabi, Yakir Rottenberg, Aviad Zick, Philip Blumenfeld, Tamar Hamburger, Eli Pikarsky, Eti Avraham, Leeby Levine, Aron Popovtzer, Tamar Yablonski-Peretz, Luna Kadouri, Hovav Nechushtan
Summary: BRCA mutations may play an oncogenic role in nonsmall cell lung cancer (NSCLC), and patients with NSCLC harboring these mutations are sensitive to poly (adenosine phosphate-ribose) polymerase inhibitors (PARPi) and platinum-based chemotherapy. Further prospective trials are needed for the treatment of NSCLC with BRCA mutations.
Review
Cardiac & Cardiovascular Systems
Kusha Rahgozar, Edwin Ho, Ythan Goldberg, Mei Chau, Azeem Latib
Summary: This article provides a comprehensive overview of transcatheter tricuspid valve interventions, including anatomy, imaging characteristics, and treatment guidelines. It summarizes the current techniques for valve repair and replacement, highlighting devices and valves under investigation.
EXPERT REVIEW OF CARDIOVASCULAR THERAPY
(2021)
Article
Oncology
Yael Laitman, Rachel Michaelson-Cohen, Rakefet Chen-Shtoyerman, Yael Goldberg, Orit Reish, Rinat Bernstein-Molho, Ephrat Levy-Lahad, Noa Ephrat Ben Baruch, Inbal Kedar, D. Gareth Evans, Sara Haim, Shani Paluch-Shimon, Eitan Friedman
Summary: Germline pathogenic sequence variants in BRCA1 significantly increase the risk of developing breast and ovarian cancer. Differences in age at diagnosis of these cancers between Ashkenazi Jews and Iraqi Jews carrying identical BRCA1 PSVs suggest the presence of ethnic-specific modifier factors.