Article
Biochemistry & Molecular Biology
Paula Francinete Faustino da Silva, Rebeca Mota Goveia, Thais Bomfim Teixeira, Bruno Faulin Gamba, Aliny Pereira de Lima, Silvia Regina Rogatto, Elisangela de Paula Silveira-Lacerda
Summary: TP53 gene mutations are associated with breast cancer. A study of 83 breast cancer patients in the Midwest region of Brazil found that 4 patients had pathogenic variants in the TP53 gene, highlighting the importance of genetic testing in this group.
Article
Oncology
Vanessa Petry, Renata Colombo Bonadio, Laura Testa, Daniela JBH. Cohn, Allyne Cagnacci, Roberta G. Campos, Maria Candida Bv Fragoso, Maria del Pilar Estevez-Diz
Summary: This study analyzed the prognosis of breast cancer in patients with germline TP53 pathogenic variants. The results showed no significant difference in recurrence-free survival and breast cancer-specific survival between patients with mTP53 and the control group.
Article
Oncology
Renata Lazari Sandoval, Natalia Polidorio, Ana Carolina Rathsam Leite, Mariana Cartaxo, Janina Pontes Pisani, Carla Vanessa Quirino, Loureno Cezana, Natalya Goncalves Pereira, Allan Andresson Lima Pereira, Benedito Mauro Rossi, Maria Isabel Achatz
Summary: The phenotype of breast cancer in Brazilian female carriers of Li-Fraumeni syndrome, particularly those with the TP53 p.R337H variant, is similar to that of carriers with other TP53 pathogenic variants. The age at onset of the disease is older than the general population but still relatively young compared to other breast cancer cases.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yaxuan Liu, Olga Axell, Tom van Leeuwen, Robert Konrat, Pedram Kharaziha, Catharina Larsson, Anthony P. H. Wright, Svetlana Bajalica-Lagercrantz
Summary: A logistic regression model was developed to predict outcomes of LFS and HBC based on the predicted effects of TP53 missense variants on protein conformation. The study found that LFS-variants were over-represented in residues buried in the core structure of TP53. The model described disease outcomes in terms of variables related to residues’ surface or buried status and their impact on protein compactness or interactions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Henriett Butz, Aniko Bozsik, Vince Grolmusz, Erika Szocs, Janos Papp, Attila Patocs
Summary: The interpretation of TP53 variants is challenging, especially in patients with attenuated LFS. A study in the Hungarian population of cancer patients found a high prevalence of pathogenic/likely pathogenic TP53 variants. The study highlights the importance of focused interpretation as automatic classification systems do not apply TP53-specific criteria.
SCIENTIFIC REPORTS
(2023)
Article
Oncology
Juraj Prejac, Natalija Dedic Plavetic, Kristina Gotovac Jercic, Fran Borovecki
Summary: Li-Fraumeni syndrome is a rare cancer predisposition syndrome caused by a germline mutation in the TP53 gene. This case report highlights a young woman with a positive family history for cancer, diagnosed with malignant solitary fibrous tumor and luminal B-like invasive breast cancer. Despite successful resection of both primary tumors, the sarcoma relapsed in the form of lung metastases, likely due to the TP53 gene variant identified through NGS analysis.
WORLD JOURNAL OF SURGICAL ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Panwen Tian, Xiaoyan Zhang, Sheng Yang, Yu Fang, Hongling Yuan, Wei Li, Honglin Zhu, Fangping Zhao, Jinlei Ding, Yunshu Zhu, Sizhen Wang, Guochen Sun, Hongbin Ni, Tonghui Ma, Ting Lei
Summary: This study retrospectively investigates P/LP TP53 germline variants (GV) among Chinese cancer patients and finds that patients with P/LP TP53 GV are mainly male and have a significantly lower median age of diagnosis compared to non-P/LP TP53 GV patients. The study also identifies one LFS patient and three LFL patients among the followed-up P/LP TP53 GV patients. Additionally, several TP53 variants are identified for the first time in Chinese LFS/LFL patients.
JOURNAL OF GENETICS AND GENOMICS
(2022)
Article
Pediatrics
Dimitrios T. Papadimitriou, Constantine A. Stratakis, Antonis Kattamis, Stavros Glentis, Constantine Dimitrakakis, George P. Spyridis, Panagiotis Christopoulos, George Mastorakos, Nikolaos F. Vlahos, Nicoletta Iacovidou
Summary: Li-Fraumeni syndrome is an autosomal dominant hereditary cancer syndrome associated with TP53 gene variants and increased risk of early-onset malignancies. A 15-month-old girl with clitoromegaly and pubic hair was diagnosed with adrenocortical carcinoma. Whole-genome sequencing revealed a novel likely pathogenic variant in the TP53 gene, confirming the diagnosis of LFS. Proper guidance led to the early detection and diagnosis of additional tumors in the patient and her mother.
Review
Oncology
Valentina Rocca, Giovanni Blandino, Lucia D'Antona, Rodolfo Iuliano, Silvia Di Agostino
Summary: Li-Fraumeni Syndrome (LFS) is a rare familial tumor predisposition syndrome caused by mutations in the TP53 gene. Patients with LFS are at risk of developing various types of tumors. This review explores the novel mechanisms of tumor onset in LFS and discusses potential treatment approaches.
Article
Oncology
Henriett Butz, Jozsef Lovey, Marton Szentkereszty, Aniko Bozsik, Erika Toth, Attila Patocs
Summary: Since the introduction of next-generation sequencing, there has been an increase in the frequency of germline pathogenic TP53 variants and cases with unusual clinical presentations. This case report presents a patient with a malignant, metastatic PEComa and sinonasal carcinoma harboring a novel TP53 germline splice mutation. Comprehensive pathological, molecular, and clinical genetic analyses were conducted, supporting the pathogenic effect of the splice mutation in the PEComa.
FRONTIERS IN ONCOLOGY
(2022)
Article
Urology & Nephrology
Kara N. Maxwell, Heather H. Cheng, Jacquelyn Powers, Roman Gulati, Elisa M. Ledet, Casey Morrison, Anh Le, Ryan Hausler, Jill Stopfer, Sophie Hyman, Wendy Kohlmann, Anne Naumer, Jennie Vagher, Samantha E. Greenberg, Lorraine Naylor, Mercy Laurino, Eric Q. Konnick, Brian H. Shirts, Saud H. AlDubayan, Eliezer M. Van Allen, Bastien Nguyen, Joseph Vijai, Wassim Abida, Maria Carlo, Marianne Dubard-Gault, Daniel J. Lee, Luke D. Maese, Diana Mandelker, Bruce Montgomery, Michael J. Morris, Piper Nicolosi, Robert L. Nussbaum, Lauren E. Schwartz, Zsofia Stadler, Judy E. Garber, Kenneth Offit, Joshua D. Schiffman, Peter S. Nelson, Oliver Sartor, Michael F. Walsh, Colin C. Pritchard
Summary: Complementary analysis of prostate cancer incidence in LFS males and gTP53 prevalence in prostate cancer cohorts suggests that gTP53 predisposes to aggressive prostate cancer. Prostate cancer should be considered as part of LFS screening protocols and TP53 should be considered in germline prostate cancer susceptibility testing.
Article
Multidisciplinary Sciences
Nicholas Light, Mehdi Layeghifard, Ayush Attery, Vallijah Subasri, Matthew Zatzman, Nathaniel D. D. Anderson, Rupal Hatkar, Sasha Blay, David Chen, Ana Novokmet, Fabio Fuligni, James Tran, Richard de Borja, Himanshi Agarwal, Larissa Waldman, Lisa M. M. Abegglen, Daniel Albertson, Jonathan L. L. Finlay, Jordan R. R. Hansford, Sam Behjati, Anita Villani, Moritz Gerstung, Ludmil B. B. Alexandrov, Gino R. R. Somers, Joshua D. D. Schiffman, Varda Rotter, David Malkin, Adam Shlien
Summary: Li-Fraumeni syndrome (LFS) is associated with pathogenic germline TP53 variants and predisposes patients to cancer. The authors analyzed 22 LFS tumors using whole-genome sequencing and reconstructed the evolution and timing of somatic driver alterations.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Ana Beatriz Sanchez-Heras, Teresa Ramon y Cajal, Marta Pineda, Elena Aguirre, Begona Grana, Isabel Chirivella, Judit Balmana, Joan Brunet
Summary: Li-Fraumeni syndrome is caused by TP53 gene heterozygous germline pathogenic variants. It is associated with a high risk of various malignant tumors in childhood and adulthood, including premenopausal breast cancer, soft tissue sarcomas and osteosarcomas, central nervous system tumors, and adrenocortical carcinomas. The concept of SLF has expanded to hereditable TP53-related cancer syndrome (hTP53rc) due to the variability of clinical manifestations, which don't always meet the classic criteria of Li-Fraumeni syndrome. Prospective studies are needed to assess genotype-phenotype characteristics and risk-adjusted recommendations.
CLINICAL & TRANSLATIONAL ONCOLOGY
(2023)
Article
Genetics & Heredity
Hiroko Fukushima, Ryoko Suzuki, Yuni Yamaki, Sho Hosaka, Masako Inaba, Wataru Morii, Emiko Noguchi, Hidetoshi Takada
Summary: This study conducted germline genetic analysis on children with RMS and identified pathogenic variants in cancer-predisposition genes, particularly a correlation between missense variants of the LIG4 gene and long-term comorbidities. Exon sequencing may be useful in elucidating the pathogenesis of RMS.
JOURNAL OF HUMAN GENETICS
(2022)
Article
Oncology
Emilia Rogoza-Janiszewska, Karolina Malinska, Bohdan Gorski, Rodney J. Scott, Cezary Cybulski, Wojciech Kluzniak, Marcin Lener, Anna Jakubowska, Jacek Gronwald, Tomasz Huzarski, Jan Lubinski, Tadeusz Debniak
Summary: This study found pathogenic TP53 variants in 4% of early-onset Polish BC patients, with no founder mutations identified in the Polish population. It is recommended to search for germline TP53 pathogenic variants in all female BC cases diagnosed at or below the age of 30 to improve treatment and surveillance screening.
Article
Oncology
Stephanie Archer, Nichola Fennell, Ellen Colvin, Rozelle Laquindanum, Meredith Mills, Romy Dennis, Francisca Stutzin Donoso, Rochelle Gold, Alice Fan, Kate Downes, James Ford, Antonis C. Antoniou, Allison W. Kurian, D. Gareth Evans, Marc Tischkowitz
Summary: This study aims to test the effectiveness of personalized risk estimates in supporting women's mental health and choices about their clinical care. It also evaluates the acceptability, feasibility, and cost-effectiveness of using personalized risk estimates in clinical care.
Article
Biochemistry & Molecular Biology
Yujeong Lee, Yoshiyuki Onishi, Lisa McPherson, Anna M. Kietrys, Marian Hebenbrock, Yong Woong Jun, Ishani Das, Shanthi Adimoolam, Debin Ji, Michael G. Mohsen, James M. Ford, Eric T. Kool
Summary: Impaired DNA repair activity is associated with increased cancer rates. This study found that certain tyrosine kinase inhibitors, such as nilotinib, can activate the repair enzyme MTH1, which cleanses oxidatively damaged nucleotides. Structural optimization resulted in compounds that strongly activate MTH1 and decrease mutagenic nucleotides in cellular DNA. These findings suggest that MTH1 activators may be a promising strategy to suppress tumorigenesis in individuals with elevated cancer risks.
ACS CHEMICAL BIOLOGY
(2022)
Article
Oncology
Alison F. Almeda, Susan M. Grimes, HoJoon Lee, Stephanie Greer, GiWon Shin, Madeline McNamara, Anna C. Hooker, Maya M. Arce, Matthew Kubit, Marie C. Schauer, Paul Van Hummelen, Cindy Ma, Meredith A. Mills, Robert J. Huang, Joo Ha Hwang, Manuel R. Amieva, Summer S. Han, James M. Ford, Hanlee P. Ji
Summary: The Gastric Cancer Registry (GCR) is a North American repository of clinical and cancer genomics data, aiming to accelerate collaborative gastric cancer research through a searchable web-based interface.
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2022)
Article
Genetics & Heredity
Winston R. Becker, Stephanie A. Nevins, Derek C. Chen, Roxanne Chiu, Aaron M. Horning, Tuhin K. Guha, Rozelle Laquindanum, Meredith Mills, Hassan Chaib, Uri Ladabaum, Teri Longacre, Jeanne Shen, Edward D. Esplin, Anshul Kundaje, James M. Ford, Christina Curtis, Michael P. Snyder, William J. Greenleaf
Summary: Single-cell ATAC-seq and RNA-seq profiling were used to study the transformation process from healthy colon to precancerous adenomas to colorectal cancer. Most of the polyp and CRC cells exhibited a stem-like phenotype. The study identified a continuum of epigenetic and transcriptional changes that occur in stem-like cells as they progress from homeostasis to CRC. The results also revealed the presence of T cell exhaustion and specific fibroblast subtypes in advanced polyps and cancerous states. Additionally, DNA methylation changes were found to be negatively correlated with accessibility changes, providing potential regulatory markers for polyp staging.
Article
Oncology
C. E. Geyer, J. E. Garber, R. D. Gelber, G. Yothers, M. Taboada, L. Ross, P. Rastogi, K. Cui, A. Arahmani, G. Aktan, A. C. Armstrong, M. Arnedos, J. Balmana, J. Bergh, J. Bliss, S. Delaloge, S. M. Domchek, A. Eisen, F. Elsafy, L. E. Fein, A. Fielding, J. M. Ford, S. Friedman, K. A. Gelmon, L. Gianni, M. Gnant, S. J. Hollingsworth, S-A Im, A. Jager, S. R. Lakhani, W. Janni, B. Linderholm, T-W Liu, N. Loman, L. Korde, S. Loibl, P. C. Lucas, F. Marme, E. Martinez de Duenas, R. McConnell, K-A Phillips, M. Piccart, G. Rossi, R. Schmutzler, E. Senkus, Z. Shao, P. Sharma, C. F. Singer, T. Spanic, E. Stickeler, M. Toi, T. A. Traina, G. Viale, G. Zoppoli, Y. H. Park, R. Yerushalmi, H. Yang, D. Pang, K. H. Jung, A. Mailliez, Z. Fan, I Tennevet, J. Zhang, T. Nagy, G. S. Sonke, Q. Sun, M. Parton, M. A. Colleoni, M. Schmidt, A. M. Brufsky, W. Razaq, B. Kaufman, D. Cameron, C. Campbell, A. N. J. Tutt, O. Th Johannsson
Summary: The OlympiA trial demonstrated that adjuvant therapy with the oral PARP inhibitor, olaparib, significantly improves overall survival in patients with gBRCA1/2pv-associated early breast cancer. The study also showed improvements in invasive disease-free survival and distant disease-free survival, with no new safety issues identified.
ANNALS OF ONCOLOGY
(2022)
Article
Oncology
Funda Meric-Bernstam, James M. Ford, Peter J. O'Dwyer, Geoffrey I. Shapiro, Lisa M. McShane, Boris Freidlin, Roisin E. O'Cearbhaill, Suzanne George, Julia Glade-Bender, Gary H. Lyman, James Tricoli, David Patton, Stanley R. Hamilton, Robert J. Gray, Douglas S. Hawkins, Bhanumati Ramineni, Keith T. Flaherty, Petros Grivas, Timothy A. Yap, Jordan Berlin, James H. Doroshow, Lyndsay N. Harris, Jeffrey A. Moscow
Summary: In the past decade, there have been multiple trials to determine the effectiveness of treating cancer based on specific genomic alterations. However, most patients do not respond to single-agent therapies targeting a single alteration, and drug resistance often develops. To address this, the NCI has developed NCI-ComboMATCH, a study to explore genomically-directed combination therapies and overcome drug resistance.
CLINICAL CANCER RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Yuan Chun Ding, Aaron W. Adamson, Mehrdad Bakhtiari, Carmina Patrick, Jonghun Park, Yael Laitman, Jeffrey N. Weitzel, Vineet Bafna, Eitan Friedman, Susan L. Neuhausen
Summary: This study investigates the role of VNTRs as causal modifiers of breast cancer risk. The results suggest that VNTRs may explain a proportion of the unexplained genetic risk for breast cancer.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Oncology
Mark E. Robson, Seock-Ah Im, Elzbieta Senkus, Binghe Xu, Susan M. Domchek, Norikazu Masuda, Suzette Delaloge, Nadine Tung, Anne Armstrong, Mike Dymond, Anitra Fielding, Allison Allen, Pierfranco Conte
Summary: In the Phase III OlympiAD study, olaparib demonstrated a significant prolongation of progression-free survival for patients with germline BRCA-mutated metastatic breast cancer, especially in those receiving it as first-line treatment. The median overall survival for olaparib was 19.3 months, compared to 17.1 months for chemotherapy treatment of physician's choice. These results suggest a potential long-term survival benefit with olaparib.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Genetics & Heredity
Elyssa Zukin, Julie O. Culver, Yuxi Liu, Yunqi Yang, Charite N. Ricker, Rachel Hodan, Duveen Sturgeon, Kerry Kingham, Nicolette M. Chun, Courtney Rowe-Teeter, Kathryn Singh, Jason A. Zell, Uri Ladabaum, Kevin J. McDonnell, James M. Ford, Giovanni Parmigiani, Danielle Braun, Allison W. Kurian, Stephen B. Gruber, Gregory E. Idos
Summary: The clinical impact of conflicting classifications of genetic variants issued by commercial laboratories was studied. Results from 2000 patients undergoing genetic testing were analyzed, and discrepancies between laboratory-provided classifications and other laboratories were identified. Only 36% of patients with conflicting classifications had a documented discussion by a provider. The study highlights the frequency of interpretation discrepancies and the importance of clinician awareness.
GENETICS IN MEDICINE
(2023)
Article
Multidisciplinary Sciences
James J. Harding, Sarina A. Piha-Paul, Ronak H. H. Shah, Jessica J. Murphy, James M. Cleary, Geoffrey I. Shapiro, David I. Quinn, Irene Brana, Victor Moreno, Mitesh Borad, Sherene Loi, Iben Spanggaard, Haeseong Park, James M. Ford, Monica Arnedos, Salomon M. Stemmer, Christelle de la Fouchardiere, Christos Fountzilas, Jie Zhang, Daniel DiPrimeo, Casey Savin, S. Duygu Selcuklu, Michael F. Berger, Lisa D. Eli, Funda Meric-Bernstam, Komal Jhaveri, David B. Solit, Ghassan K. Abou-Alfa
Summary: In patients with biliary tract cancer, HER2 alterations correlate with poor prognosis. A phase II clinical trial showed that the tyrosine kinase inhibitor neratinib has some efficacy in treating advanced biliary tract cancers with HER2-mutation positive. The objective response rate to neratinib was 16% (95% CI 4.5-36.1%).
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Laura Westbrook, Darlene Miltenburg, Vivienne Souter, Melissa K. Maisenbacher, Katherine L. Howard, Youbao Sha, Maygol Yavari, Nicholas Kypraios, Angel Rodriguez, Jeffrey N. Weitzel
Summary: This study aimed to determine the yield of hereditary cancer gene pathogenic variants among diverse women attending breast imaging centers, who could benefit from enhanced surveillance and/or risk reduction interventions.
BREAST CANCER RESEARCH AND TREATMENT
(2023)
Article
Oncology
Lauren Lenz, Chris Neff, Cara Solimeno, Elizabeth S. Cogan, Vandana G. Abramson, Judy C. Boughey, Carla Falkson, Matthew P. Goetz, James M. Ford, William J. Gradishar, Rachel C. Jankowitz, Virginia G. Kaklamani, P. Kelly Marcom, Andrea L. Richardson, Anna Maria Storniolo, Nadine M. M. Tung, Shaveta Vinayak, Darren R. Hodgson, Zhongwu Lai, Simon Dearden, Bryan T. Hennessy, Erica L. Mayer, Gordon B. Mills, Thomas P. Slavin, Alexander Gutin, Roisin M. Connolly, Melinda L. Telli, Vered Stearns, Jerry S. Lanchbury, Kirsten M. Timms
Summary: This study evaluated whether the genomic instability score (GIS) distributions of BRCA1/2-deficient estrogen receptor-positive breast cancer (ER + BC) and triple-negative breast cancer (TNBC) are similar to that of ovarian cancer. The results showed that the GIS distribution of BRCA1/2-deficient samples was lower in ER + BC compared to ovarian cancer, but there was no significant difference in TNBC. In TNBC patients, the GIS thresholds were validated using clinical response data to platinum therapy.
BREAST CANCER RESEARCH AND TREATMENT
(2023)
Editorial Material
Oncology
Minna K. Lee, Mark E. Robson
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2023)
Article
Oncology
Nicholas C. Turner, A. Douglas Laird, Melinda L. Telli, Hope S. Rugo, Audrey Mailliez, Johannes Ettl, Eva-Maria Grischke, Lida A. Mina, Judith Balmana, Peter A. Fasching, Sara A. Hurvitz, Julia F. Hopkins, Lee A. Albacker, Jijumon Chelliserry, Ying Chen, Umberto Conte, Andrew M. Wardley, Mark E. Robson
Summary: These analyses investigate the impact of homologous recombination repair gene mutations, including BRCA1/2 mutations and homologous recombination deficiency (HRD), on the efficacy of the PARP inhibitor talazoparib in the ABRAZO trial. The study finds that BRCA mutations and HRD have a significant effect on the efficacy of talazoparib in germline BRCA1/2-mutation carriers. The presence of BRCA1/2 mutations and loss of heterozygosity at BRCA locus indicate HRD. Non-BRCA tumor mutations, such as TP53 and PIK3CA, are also associated with specific BRCA mutations.
Article
Oncology
Ana Beatriz Sanchez-Heras, Teresa Ramon y Cajal, Marta Pineda, Elena Aguirre, Begona Grana, Isabel Chirivella, Judit Balmana, Joan Brunet
Summary: Li-Fraumeni syndrome is caused by TP53 gene heterozygous germline pathogenic variants. It is associated with a high risk of various malignant tumors in childhood and adulthood, including premenopausal breast cancer, soft tissue sarcomas and osteosarcomas, central nervous system tumors, and adrenocortical carcinomas. The concept of SLF has expanded to hereditable TP53-related cancer syndrome (hTP53rc) due to the variability of clinical manifestations, which don't always meet the classic criteria of Li-Fraumeni syndrome. Prospective studies are needed to assess genotype-phenotype characteristics and risk-adjusted recommendations.
CLINICAL & TRANSLATIONAL ONCOLOGY
(2023)