Article
Biochemistry & Molecular Biology
Bryndis Yngvadottir, Avgi Andreou, Laia Bassaganyas, Alexey Larionov, Alex J. Cornish, Daniel Chubb, Charlie N. Saunders, Philip Smith, Huairen Zhang, Yasemin Cole, James Larkin, Lisa Browning, Samra Turajlic, Kevin Litchfield, Richard S. Houlston, Eamonn R. Maher
Summary: In unselected RCC patients, approximately 6% carry germline variants that require further follow-up analysis. Expanding the genomic panel for RCC susceptibility gene testing can improve diagnostic yield.
HUMAN MOLECULAR GENETICS
(2022)
Article
Oncology
Semanti Mukherjee, Chaitanya Bandlamudi, Matthew D. Hellmann, Yelena Kemel, Esther Drill, Hira Rizvi, Kaitlyn Tkachuk, Aliya Khurram, Michael F. Walsh, Marjorie G. Zauderer, Diana Mandelker, Sabine Topka, Ahmet Zehir, Preethi Srinivasan, Myvizhi Esai Selvan, Maria I. Carlo, Karen A. Cadoo, Alicia Latham, Jada G. Hamilton, Ying L. Liu, Steven M. Lipkin, Sami Belhadj, Gareth L. Bond, Zeynep H. Gumus, Robert J. Klein, Marc Ladanyi, David B. Solit, Mark E. Robson, David R. Jones, Mark G. Kris, Joseph Vijai, Zsofia K. Stadler, Christopher I. Amos, Barry S. Taylor, Michael F. Berger, Charles M. Rudin, Kenneth Offit
Summary: This study found that germline pathogenic/likely pathogenic variants (PV) in lung cancer predisposing genes are associated with a higher risk of developing lung cancer. These variants, particularly in DNA damage repair (DDR) pathway genes, are closely related to biallelic inactivation in tumors. It also revealed that patients with germline PV in lung cancer predisposing genes tend to be diagnosed at a younger age, and high-risk patients are more likely to carry germline PV.
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2022)
Article
Oncology
Li Hu, Jie Sun, Zhongwu Li, Ziwei Qu, Yan Liu, Qiting Wan, Jiaming Liu, Xinyun Ding, Fan Zang, Juan Zhang, Lu Yao, Ye Xu, Yin Wang, Yuntao Xie
Summary: The prevalence and clinical relevance of pathogenic germline variants in MMR genes in Chinese breast cancer patients were investigated. MMR variant carriers had worse survival and some might benefit from immunotherapy.
Article
Andrology
Huayi Feng, Shouqing Cao, Qing Ouyang, Huaikang Li, Xiubin Li, Ke Chen, Xiangyi Zhang, Yan Huang, Xu Zhang, Xin Ma
Summary: Thirteen out of 123 patients with renal cell carcinoma (RCC) had pathogenic or likely pathogenic germline mutations in 10 cancer predisposition genes, including FANCI and FANCM. Patients with these mutations tended to have an earlier onset of RCC and were more likely to have bilateral or multifocal RCC. Non-clear cell RCC patients were significantly more likely to have RCC-associated gene mutations.
TRANSLATIONAL ANDROLOGY AND UROLOGY
(2023)
Article
Genetics & Heredity
Maria Santos, Javier Lanillos, Juan Maria Roldan-Romero, Eduardo Caleiras, Cristina Montero-Conde, Alberto Cascon, Miguel Angel Climent, Georgia Anguera, Susana Hernando, Nuria Lainez, Mercedes Robledo, Luis Robles, Guillermo de Velasco, Jesus Garcia-Donas, Cristina Rodriguez-Antona
Summary: The study found a high prevalence of pathogenic germline variants in RCC predisposition genes in metastatic non-ccRCC, especially in patients with papillary type 2 or unconventional histologies compatible with FH. Genetic screening may benefit these metastatic patients.
GENETICS IN MEDICINE
(2021)
Article
Medicine, General & Internal
Lingdi Yin, Jishu Wei, Zipeng Lu, Shimeng Huang, Hao Gao, Jianmin Chen, Feng Guo, Min Tu, Bin Xiao, Chunhua Xi, Kai Zhang, Qiang Li, Junli Wu, Wentao Gao, Kuirong Jiang, Jun Yu, Yi Miao
Summary: A higher incidence of pancreatic cancer has been reported in the Chinese population compared with the White population, and genetic background of pancreatic cancer in the Han Chinese population with PDAC was explored in this study, revealing a significant association between pathogenic germline variations and sporadic pancreatic cancer in China.
Article
Oncology
Wen Kong, Tongtong Yang, Xiaodong Wen, Zhongyi Mu, Cheng Zhao, Sujun Han, Jing Tian, Xinhao Zhang, Tao Zhou, Yanrui Zhang, Feng Lou, Shanbo Cao, Huina Wang, Jin Zhang
Summary: Approximately 10% of RCC patients carry clinically significant germline mutations, with syndromic RCC-associated gene variants mainly found in young patients and variants in other cancer-predisposition genes more common in patients over 46 years old. Germline and somatic sequencing have provided potentially actionable therapeutic targets for a subset of patients.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Belle W. X. Lim, Na Li, Sakshi Mahale, Simone M. McInerny, Magnus Zethoven, Simone M. Rowley, Joanne Huynh, Theresa Wang, Jue Er Amanda Lee, Mia Friedman, Lisa Devereux, Rodney J. Scott, Erica K. Sloan, Paul A. James, Ian G. Campbell
Summary: This study found that BARD1 and RAD51D behave as classic BRCA-like predisposition genes with biallelic loss in breast cancer. In contrast to other breast cancer-related genes, CHEK2 gene lacks biallelic loss, but this does not definitively exclude its involvement in breast cancer predisposition.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2023)
Article
Oncology
Hiroko Kimura, Kei Mizuno, Masaki Shiota, Shintaro Narita, Naoki Terada, Naohiro Fujimoto, Keiji Ogura, Shotaro Hatano, Yusuke Iwasaki, Nozomi Hakozaki, Satoshi Ishitoya, Takayuki Sumiyoshi, Takayuki Goto, Takashi Kobayashi, Hidewaki Nakagawa, Toshiyuki Kamoto, Masatoshi Eto, Tomonori Habuchi, Osamu Ogawa, Yukihide Momozawa, Shusuke Akamatsu
Summary: Germline variants in BRCA1, BRCA2, PALB2, or ATM are independent prognostic factors for the short duration of response to hormonal therapy in advanced prostate cancer.
BRITISH JOURNAL OF CANCER
(2022)
Article
Oncology
Burcu F. Darst, Tokhir Dadaev, Ed Saunders, Xin Sheng, Peggy Wan, Loreall Pooler, Lucy Y. Xia, Stephen Chanock, Sonja Berndt, Susan M. Gapstur, Victoria Stevens, Demetrius Albanes, Stephanie J. Weinstein, Vincent Gnanapragasam, Graham G. Giles, Tu Nguyen-Dumont, Roger L. Milne, Mark Pomerantz, Julie A. Schmidt, Lorelei Mucci, William J. Catalona, Kurt N. Hetrick, Kimberly F. Doheny, Robert J. MacInnis, Melissa C. Southey, Rosalind A. Eeles, Fredrik Wiklund, Zsofia Kote-Jarai, David Conti, Christopher A. Haiman
Summary: The study identified a significant association between rare P/LP/D alleles in DNA repair genes such as BRCA2, PALB2, and ATM with aggressive prostate cancer risk, highlighting the importance of these genes in both screening and disease management considerations.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2021)
Article
Medicine, General & Internal
Geoffrey Y. Ku, Yelena Kemel, Steve B. Maron, Joanne F. Chou, Vignesh Ravichandran, Zarina Shameer, Anna Maio, Elizabeth S. Won, David P. Kelsen, David H. Ilson, Marinela Capanu, Vivian E. Strong, Daniela Molena, Smita Sihag, David R. Jones, Daniel G. Coit, Yaelle Tuvy, Kendall Cowie, David B. Solit, Nikolaus Schultz, Jaclyn F. Hechtman, Kenneth Offit, Vijai Joseph, Diana Mandelker, Yelena Y. Janjigian, Zsofia K. Stadler
Summary: The study revealed a higher prevalence of pathogenic germline alterations in patients with esophagogastric cancer, particularly in gastric cancer and early-onset cases. This suggests the importance of genetic testing in these populations for identifying potential hereditary cancer syndromes.
Article
Oncology
Jean-Noel Hubert, Voreak Suybeng, Maxime Vallee, Tiffany M. Delhomme, Eve Maubec, Anne Boland, Delphine Bacq, Jean-Francois Deleuze, Fanelie Jouenne, Paul Brennan, James D. McKay, Marie-Francoise Avril, Brigitte Bressac-de Paillerets, Estelle Chanudet
Summary: The study reveals genetic predispositions in patients with malignant melanoma and renal cell carcinoma through a comprehensive exploration of coding genes, identifying 13 novel susceptibility candidates. This contributes to a better understanding and diagnosis of these cancers, essential for clinical management.
Article
Medicine, General & Internal
Chunling Hu, Steven N. Hart, Rohan Gnanaolivu, Hongyan Huang, Kun Y. Lee, Jie Na, Chi Gao, Jenna Lilyquist, Siddhartha Yadav, Nicholas J. Boddicker, Raed Samara, Josh Klebba, Christine B. Ambrosone, Hoda Anton-Culver, Paul Auer, Elisa V. Bandera, Leslie Bernstein, Kimberly A. Bertrand, Elizabeth S. Burnside, Brian D. Carter, Heather Eliassen, Susan M. Gapstur, Mia Gaudet, Christopher Haiman, James M. Hodge, David J. Hunter, Eric J. Jacobs, Esther M. John, Charles Kooperberg, Allison W. Kurian, Loic Le Marchand, Sara Lindstroem, Tricia Lindstrom, Huiyan Ma, Susan Neuhausen, Polly A. Newcomb, Katie M. O'Brien, Janet E. Olson, Irene M. Ong, Tuya Pal, Julie R. Palmer, Alpa V. Patel, Sonya Reid, Lynn Rosenberg, Dale P. Sandler, Christopher Scott, Rulla Tamimi, Jack A. Taylor, Amy Trentham-Dietz, Celine M. Vachon, Clarice Weinberg, Song Yao, Argyrios Ziogas, Jeffrey N. Weitzel, David E. Goldgar, Susan M. Domchek, Katherine L. Nathanson, Peter Kraft, Eric C. Polley, Fergus J. Couch
Summary: This study provides population-based estimates of the prevalence and risk of breast cancer associated with pathogenic variants in known cancer-predisposition genes. The results highlight the varying levels of risk associated with different genes, such as high risk for BRCA1 and BRCA2 and moderate risk for PALB2, as well as associations with specific subtypes of breast cancer for genes like RAD51C and RAD51D.
NEW ENGLAND JOURNAL OF MEDICINE
(2021)
Article
Cell Biology
Sarah Abou Alaiwi, Amin H. Nassar, Elio Adib, Stefan M. Groha, Elie W. Akl, Bradley A. McGregor, Edward D. Esplin, Shan Yang, Kathryn Hatchell, Vincent Fusaro, Sarah Nielsen, David J. Kwiatkowski, Guru P. Sonpavde, Mark Pomerantz, Judy E. Garber, Matthew L. Freedman, Huma Q. Rana, Alexander Gusev, Toni K. Choueiri
Summary: This study examined the germline landscape of 1,829 RCC patients from diverse ancestries and found 17% of patients carrying pathogenic and likely pathogenic variants, with 10.3% having potentially actionable variants. Differences in variant frequencies were observed between African and non-African patients, with non-African patients having more actionable variants. This research sheds light on biological disparities in RCC between African and non-African populations and may lead to more comprehensive genomic studies in underrepresented populations.
Article
Oncology
Junlong Wu, Yu Wei, Jian Pan, Shengming Jin, Weijie Gu, Hualei Gan, Yao Zhu, Ding-Wei Ye
Summary: This study provides a comprehensive view of germline DDR gene mutations in PCa patients and identifies two potential PCa predisposition genes, POLN and POLG, not previously reported in the Western population, highlighting the necessity of customizing a multigene panel for Chinese PCa patients.
INTERNATIONAL JOURNAL OF CANCER
(2021)
Article
Oncology
Rajiv Agarwal, Paul Shin, Andrea Knezevic, Judith E. Nelson, Danielle R. Romano, Camila Bernal, Anjali Desai, Andrew S. Epstein
Summary: This study assessed the accuracy of cure expectations in gastrointestinal cancer patients and found that inaccurate expectations were prevalent across all stages of the disease, particularly in those with metastatic or unresectable cancer. The accuracy was lower in advanced stages and higher in early-stage patients who received adjuvant chemotherapy. Hospitalization and location of death also had an impact on accuracy.
Article
Urology & Nephrology
Hong Truong, Kelsey Breen, Subhiksha Nandakumar, Daniel D. Sjoberg, Yelena Kemel, Nikita Mehta, Andrew T. Lenis, Peter A. Reisz, Jessica Carruthers, Nicole Benfante, Vijai Joseph, Aliya Khurram, Anuradha Gopalan, Samson W. Fine, Victor E. Reuter, Andrew J. Vickers, Ozge Birsoy, Ying Liu, Michael Walsh, Alicia Latham, Zsofia K. Stadler, Eugene Pietzak, Behfar Ehdaie, Karim A. Touijer, Vincent P. Laudone, Susan F. Slovin, Karen A. Autio, Daniel C. Danila, Dana E. Rathkopf, James A. Eastham, Yu Chen, Michael J. Morris, Kenneth Offit, David B. Solit, Howard I. Scher, Wassim Abida, Mark E. Robson, Maria I. Carlo
Summary: Tumor-only genomic profiling can help identify germline variants in prostate cancer patients, providing important information for genetic counseling and prioritizing genetic testing.
Article
Oncology
Sami Belhadj, Aliya Khurram, Chaitanya Bandlamudi, Guillermo Palou-Marquez, Vignesh Ravichandran, Zoe Steinsnyder, Temima Wildman, Amanda Catchings, Yelena Kemel, Semanti Mukherjee, Benjamin Fesko, Kanika Arora, Miika Mehine, Sita Dandiker, Aalin Izhar, John Petrini, Susan Domchek, Katherine L. Nathanson, Jamie Brower, Fergus Couch, Zsofia Stadler, Mark Robson, Michael Walsh, Joseph Vijai, Michael Berger, Fran Supek, Rachid Karam, Sabine Topka, Kenneth Offit
Summary: Through sequencing analysis of matched germline and somatic DNA samples from 34,046 patients, 32 pathogenic variants of NBN were identified. Patients carrying these variants showed increased loss of wild-type allele in lung and pancreatic tumors. Functional studies confirmed the important role of NBN in a broad spectrum of cancers.
CLINICAL CANCER RESEARCH
(2023)
Article
Urology & Nephrology
Kelly N. Fitzgerald, Cihan Duzgol, Andrea Knezevic, Natalie Shapnik, Ritesh Kotecha, David H. Aggen, Maria I. Carlo, Neil J. Shah, Martin H. Voss, Darren R. Feldman, Robert J. Motzer, Chung -Han Lee
Summary: There is no significant difference in outcomes between immunotherapy-based combinations and tyrosine kinase inhibitor/immune checkpoint inhibitor combination in the treatment of metastatic clear cell renal cell carcinoma (ccRCC), suggesting that the current treatment strategy should not be changed.
Article
Oncology
Jonathan A. Coleman, Wesley Yip, Nathan C. Wong, Daniel D. Sjoberg, Bernard H. Bochner, Guido Dalbagni, S. Machele Donat, Harry W. Herr, Eugene K. Cha, Timothy F. Donahue, Eugene J. Pietzak, A. Ari Hakimi, Kwanghee Kim, Hikmat A. Al-Ahmadie, H. Alberto Vargas, Ricardo G. Alvim, Soleen Ghafoor, Nicole E. Benfante, Anoop M. Meraney, Steven J. Shichman, Jeffrey M. Kamradt, Suresh G. Nair, Angelo A. Baccala, Paul Palyca, Bradley W. Lash, Muhammad A. Rizvi, Scott K. Swanson, Antonio F. Muina, Andrea B. Apolo, Gopa Iyer, Jonathan E. Rosenberg, Min Y. Teo, Dean F. Bajorin
Summary: Neoadjuvant chemotherapy with split-dose GC has positive effects on pathologic response and favorable survival outcomes for patients with high-risk UTUC.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Urology & Nephrology
Kelly N. Fitzgerald, Robert J. Motzer, Chung-Han Lee
Summary: Localized renal cell carcinoma is usually treated with nephrectomy, but recurrence is still common. Adjuvant therapies are used to disrupt the metastatic cascade and potentially cure more patients. Immune checkpoint inhibitors and VEGFR-targeting TKIs have shown efficacy in the treatment of metastatic RCC, leading to interest in their use in the adjuvant setting.
NATURE REVIEWS UROLOGY
(2023)
Article
Oncology
Sushmita Gordhandas, Eric Rios-Doria, Karen A. Cadoo, Amanda Catchings, Anna Maio, Yelena Kemel, Margaret Sheehan, Megha Ranganathan, Dina Green, Anjali Aryamvally, Angela G. Arnold, Erin Salo-Mullen, Beryl Manning-Geist, Tiffany Sia, Pier Selenica, Arnaud Da Cruz Paula, Chad Vanderbilt, Maksym Misyura, Mario M. Leitao, Jennifer J. Mueller, Vicky Makker, Maria Rubinstein, Claire F. Friedman, Qin Zhou, Alexia Iasonos, Alicia Latham, Maria Carlo, Yonina R. Murciano-Goroff, Marie Will, Michael F. Walsh, Shirin Issa Bhaloo, Lora H. Ellenson, Ozge Ceyhan-Birsoy, Michael F. Berger, Mark E. Robson, Nadeem Abu-Rustum, Carol Aghajanian, Kenneth Offit, Zsofia Stadler, Britta Weigelt, Diana L. Mandelker, Ying L. Liu
Summary: This study investigated the prevalence of germline pathogenic variants in patients with endometrial cancer, and found that 13% of patients had such variants, with 63% of high-penetrance genes exhibiting biallelic inactivation, potentially driving cancer development. The results support the importance of germline assessment in endometrial cancer for treatment and cancer prevention.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2023)
Article
Oncology
Michael B. Foote, Henry Walch, Yelena Kemel, Efsevia Vakiani, Paul Johannet, Margaret Sheehan, Walid Chatila, Sebastian Chung, Garrett M. Nash, Anna Maio, Jinru Shia, Diana Mandelker, Michael Berger, Nikolaus Schultz, Luis A. Diaz, Andrea Cercek, Zsofia K. Stadler
Summary: Over 10% of patients with appendiceal adenocarcinoma have pathogenic or likely pathogenic germline variants. This study evaluated the clinical and molecular impact of heritable alterations in appendiceal adenocarcinoma to determine the need for dedicated screening and prevention strategies.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Ying L. Liu, Beryl L. Manning-Geist, Andrea Knezevic, Luxue Deng, Maria Bromberg, Samuel A. Funt, Jane L. Meisel, Oliver Zivanovic, Kara Long Roche, Yukio Sonoda, Ginger J. Gardner, Rachel N. Grisham, Roisin E. O'Cearbhaill, William P. Tew, Nadeem R. Abu-Rustum, Dennis S. Chi, Carol Aghajanian, Darren R. Feldman
Summary: The objective of this study was to validate the modified international male IGCCCG prognostic model in female patients with germ cell tumors (GCTs). The results demonstrated that the modified IGCCCG model accurately assessed the prognostic risk in female GCTs patients and was associated with clinical outcomes.
GYNECOLOGIC ONCOLOGY
(2023)
Article
Oncology
Ritesh R. Kotecha, Andrea Knezevic, Kanika Arora, Chaitanya Bandlamudi, Fengshen Kuo, Maria I. Carlo, Kelly N. Fitzgerald, Darren R. Feldman, Neil J. Shah, Ed Reznik, A. Ari Hakimi, Jian Carrot-Zhang, Diana Mandelker, Michael Berger, Chung-Han Lee, Robert J. Motzer, Martin H. Voss
Summary: This study examines the differences in clinical and molecular data among different genetic ancestry groups in patients with renal cell carcinoma (RCC). The findings suggest that genetic ancestry may contribute to variations in clinical and molecular characteristics of RCC, and significant differences were identified in angiogenesis and inflammatory pathways. This study highlights the importance of exploring both genetic and nongenetic variables in order to reduce health-related disparities.
Article
Oncology
Samuel A. Funt, Andrea Knezevic, Kaamilah Wilson, Maria Bromberg, Amy Budnick, Kerri L. O'Connor, Deaglan J. Mchugh, Erik Larsen, Dean F. Bajorin, Robert J. Motzer, Emily S. Tonorezos, Sujata Patil, Darren R. Feldman
Summary: This study confirms the hearing impairment caused by high-dose carboplatin in GCT patients, with most patients experiencing moderate to profound HL in the speech frequencies.
Meeting Abstract
Oncology
Darren R. Feldman, Robert J. Motzer, Andrea Knezevic, Chung-Han Lee, Martin H. Voss, Serge K. Lyashchenko, Hijin Park, Steven M. Larson, Neeta Pandit-Taskar
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Meeting Abstract
Oncology
Kelly N. Fitzgerald, Cihan Duzgol, Andrea Knezevic, Natalie Shapnik, Ritesh R. Kotecha, David H. Aggen, Maria Isabel Carlo, Neil J. Shah, Martin H. Voss, Darren R. Feldman, Robert J. Motzer, Chung-Han Lee
JOURNAL OF CLINICAL ONCOLOGY
(2023)