Article
Gastroenterology & Hepatology
Toky Ratovomanana, Romain Cohen, Magali Svrcek, Florence Renaud, Pascale Cervera, Aurelie Siret, Quentin Letourneur, Olivier Buhard, Pierre Bourgoin, Erell Guillerm, Coralie Dorard, Remy Nicolle, Mira Ayadi, Mehdi Touat, Franck Bielle, Marc Sanson, Philippe Le Rouzic, Marie-Pierre Buisine, Guillaume Piessen, Ada Collura, Jean-Francois Flejou, Aurelien de Reynies, Florence Coulet, Francois Ghiringhelli, Thierry Andre, Vincent Jonchere, Alex Duval
Summary: This study evaluated the performance of NGS in identifying MSI in CRC, especially dMMR mCRC treated with ICI, and proposed a new algorithm called MSICare. The results showed that MSICare performed more accurately in detecting MSI in all testing modes, making it a potential reference method for NGS-based testing of MSI in CRC, especially in mCRC requiring ICI treatment.
Review
Biochemistry & Molecular Biology
Martina Amato, Renato Franco, Gaetano Facchini, Raffaele Addeo, Fortunato Ciardiello, Massimiliano Berretta, Giulia Vita, Alessandro Sgambato, Sandro Pignata, Michele Caraglia, Marina Accardo, Federica Zito Marino
Summary: Microsatellite instability (MSI) is common in cancer and predicts sensitivity to immune checkpoint inhibitors. Different MSI testing methods are used in clinical practice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pathology
Ngome L. Makia, Martha Thomas, Kari L. Ring, Christopher A. Moskaluk, Anne M. Mills
Summary: Immunostaining is useful for screening Lynch syndrome, but can also identify MMR-deficient tumors without germline pathogenic variants. Understanding the frequency of somatic MMR pathogenic variants in tumors with MMR immunohistochemical loss and normal germline testing is important for prognosis and immune checkpoint inhibitor treatment. This study found that correctly interpreted immunohistochemistry is a reliable surrogate for somatic MMR pathogenic variants in endometrial cancer, supporting its use as the frontline MMR biomarker.
AMERICAN JOURNAL OF SURGICAL PATHOLOGY
(2023)
Article
Oncology
Raphael Colle, Anna Radzik, Romain Cohen, Anna Pellat, Daniel Lopez-Tabada, Marine Cachanado, Alex Duval, Magali Svrcek, Yves Menu, Thierry Andre
Summary: The study found that 10% of patients with MSI/dMMR mCRC treated with ICIs experienced PSPD, with most of them occurring within the first 3 months, representing the majority of primary radiological PDs. There were almost no occurrences of PSPD after 3 months.
EUROPEAN JOURNAL OF CANCER
(2021)
Article
Oncology
Camilla Di Dio, Giorgio Bogani, Violante Di Donato, Ilaria Cuccu, Ludovico Muzii, Lucia Musacchio, Giovanni Scambia, Domenica Lorusso
Summary: Endometrial cancer is a heterogeneous disease with specific genomic, molecular, and biological features. Immune checkpoint inhibitors and tyrosine kinase inhibitors have shown promising results in the treatment of advanced or recurrent endometrial cancer. The combination of pembrolizumab and lenvatinib has become the new standard second-line treatment, regardless of the MMR status. Further studies are exploring the use of immune checkpoint inhibitors and PARP inhibitors in combination therapy.
GYNECOLOGIC ONCOLOGY
(2023)
Article
Pathology
So Young Kang, Deok Geun Kim, Soomin Ahn, Sang Yun Ha, Kee-Taek Jang, Kyoung-Mee Kim
Summary: Checkpoint inhibitor approval for microsatellite instability-high (MSI-H) tumors has made MSI a therapeutically important biomarker. Next-generation sequencing (NGS)-based MSI detection is being widely used, but its relevance to MSI-PCR and mismatch repair deficiency (dMMR) is unclear. In this study, NGS-MSI results were compared with MSI-PCR and MMR IHC results to define cut-off points for MSI in order to facilitate therapeutic decision-making.
PATHOLOGY RESEARCH AND PRACTICE
(2022)
Article
Biochemical Research Methods
Koen Swaerts, Franceska Dedeurwaerdere, Dieter De Smet, Peter De Jaeger, Geert A. A. Martens
Summary: This study aimed to use machine learning to process the complexity of indel distributions and integrate it into a robust script for dMMR screening on small gene panel-based NGS data of clinical tumor samples. The results showed that the novel script (DeltaMSI) achieved higher robustness and diagnostic power compared to the widely used script mSINGS, indicating its clinical potential for high-throughput MSI screening in all tumor types.
BMC BIOINFORMATICS
(2023)
Article
Oncology
Birgit S. Geurts, Thomas W. Battaglia, J. Maxime van Berge Henegouwen, Laurien J. Zeverijn, Gijs F. de Wit, Louisa R. Hoes, Hanneke van der Wijngaart, Vincent van der Noort, Paul Roepman, Wendy W. J. de Leng, Anne M. L. Jansen, Frans L. Opdam, Maja J. A. de Jonge, Geert A. Cirkel, Mariette Labots, Ann Hoeben, Emile D. Kerver, Adriaan D. Bins, Frans G. L. Erdkamp, Johan M. van Rooijen, Danny Houtsma, Mathijs P. Hendriks, Jan-Willem B. de Groot, Henk M. W. Verheul, Hans Gelderblom, Emile E. Voest
Summary: In this study, the efficacy and safety of the PD-L1 inhibitor durvalumab were evaluated in patients with mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) tumors. Durvalumab showed good tolerability and provided durable responses in these patients who had exhausted standard treatment options.
Article
Oncology
Ziyu Li, Yongning Jia, Honglin Zhu, Hongling Yuan, Xiaofang Xing, Yaqun Xin, Tonghui Ma, Fei Pang, Yan Zhang, Ying Hu, Shuqin Jia, Jiafu Ji
Summary: A novel method combining MSI score, MMR mutation status and TMB level was developed to identify MSI status from NGS data. High MSI was found in 1.84% of samples across 30 cancer types in Chinese patients, and was associated with high TMB, PD-L1 expression and tumor-infiltrating immune cells.
INTERNATIONAL JOURNAL OF CANCER
(2022)
Article
Oncology
M. Maio, P. A. Ascierto, L. Manzyuk, D. Motola-Kuba, N. Penel, P. A. Cassier, G. M. Bariani, A. De Jesus Acosta, T. Doi, F. Longo, W. H. Jr Jr Miller, D-Y Oh, M. Gottfried, L. Xu, F. Jin, K. Norwood, A. Marabelle
Summary: Pembrolizumab has shown clinically meaningful and durable efficacy in previously treated advanced MSI-H/dMMR noncolorectal cancers, with a high ORR of 30.8%, a median duration of response of 47.5 months, and manageable safety.
ANNALS OF ONCOLOGY
(2022)
Review
Oncology
Romain Cohen, Raphael Colle, Thomas Pudlarz, Maximilien Heran, Alex Duval, Magali Svrcek, Thierry Andre
Summary: Microsatellite instability (MSI) is a tumor phenotype related to a deficient DNA mismatch repair system (dMMR). This phenotype, observed in 5% of metastatic mCRC but 10-18% of localized CRC, is associated with high tumor mutational burden with highly immunogenic neoantigens. It has emerged as a major predictive biomarker for the efficacy of ICIs.
Review
Oncology
Jeremy Setton, Michael Zinda, Nadeem Riaz, Daniel Durocher, Michal Zimmermann, Maria Koehler, Jorge S. Reis-Filho, Simon N. Powell
Summary: Synthetic lethality (SL) provides a theoretical framework for targeting loss-of-function mutations in tumor suppressor genes and DNA repair genes, as well as amplification and/or overexpression of genes that cannot be directly targeted. The emergence of next generation tumor-specific alterations targetable through SL from high-throughput CRISPR technology presents new opportunities for drug development, but also brings important challenges in developing optimal predictive biomarkers.
Article
Oncology
Ana Claudia Marques, Carole Ferraro-Peyret, Frederic Michaud, Lin Song, Ewan Smith, Guillaume Fabre, Adrian Willig, Melissa M. L. Wong, Xiaobin Xing, Chloe Chong, Marion Brayer, Tanguy Fenouil, Valerie Hervieu, Brigitte Bancel, Mojgan Devouassoux, Brigitte Balme, David Meyronet, Philippe Menu, Jonathan Lopez, Zhenyu Xu
Summary: MSIdetect is a novel NGS-based MSI detection method that models the impact of indel burden and tumor content on read coverage at homopolymer regions, demonstrating high specificity and sensitivity. This method successfully addresses the challenges of MSI detection from tumor-only data.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Quang Loc Bui, Leo Mas, Antoine Hollebecque, David Tougeron, Christelle de la Fouchardiere, Thomas Pudlarz, Emily Alouani, Rosine Guimbaud, Julien Taieb, Thierry Andre, Raphael Colle, Romain Cohen
Summary: This study retrospectively collected clinical data from 31 patients with dMMR/MSI mCRC. The results showed that there was no improved outcome with CT after ICI failure, but prolonged disease control was observed in some cases.
Review
Biochemistry & Molecular Biology
Andrea Palicelli, Stefania Croci, Alessandra Bisagni, Eleonora Zanetti, Dario De Biase, Beatrice Melli, Francesca Sanguedolce, Moira Ragazzi, Magda Zanelli, Alcides Chaux, Sofia Canete-Portillo, Maria Paola Bonasoni, Stefano Ascani, Antonio De Leo, Guido Giordano, Matteo Landriscina, Giuseppe Carrieri, Luigi Cormio, Jatin Gandhi, Davide Nicoli, Enrico Farnetti, Simonetta Piana, Alessandro Tafuni, Martina Bonacini
Summary: This study reviewed the potential correlations between PD-L1 and MMR/MSI/BRCA/PTEN statuses in prostate cancer and discussed several other relevant genes. The results showed that some patients can be treated with specific antibody drugs. Further research is needed to verify the efficacy of these treatment methods and the relationship with the related factors.