scispace - formally typeset
Search or ask a question
Author

Shaleigh A. Smith

Bio: Shaleigh A. Smith is an academic researcher from Memorial Sloan Kettering Cancer Center. The author has contributed to research in topics: Germline & Cancer. The author has an hindex of 1, co-authored 3 publications receiving 4 citations.

Papers
More filters
Posted ContentDOI
Bastien Nguyen1, Christopher J. Fong1, Anisha Luthra1, Shaleigh A. Smith1, Renzo G. DiNatale2, Renzo G. DiNatale3, Subhiksha Nandakumar1, Henry Walch1, Walid K. Chatila1, Ramyasree Madupuri1, Ritika Kundra1, Craig M. Bielski4, Craig M. Bielski1, Brooke Mastrogiacomo1, Adrienne Boire1, Sarat Chandarlapaty1, Karuna Ganesh2, Karuna Ganesh1, James J. Harding1, James J. Harding4, Christine A. lacobuzio-Donahue1, Pedram Razavi4, Pedram Razavi1, Ed Reznik1, Charles M. Rudin1, Charles M. Rudin2, Dmitriy Zamarin4, Dmitriy Zamarin1, Wassim Abida1, Ghassan K. Abou-Alfa1, Carol Aghajanian1, Andrea Cercek1, Ping Chi1, Darren R. Feldman1, Alan L. Ho1, Gopakumar Iyer1, Yelena Y. Janjigian1, Michael J. Morris1, Robert J. Motzer1, Eileen M. O'Reilly1, Michael A. Postow1, Nitya Raj1, Gregory J. Riely1, Mark E. Robson1, Jonathan E. Rosenberg1, Anton Safonov1, Alexander N. Shoushtari1, William D. Tap1, Min Yuen Teo1, Anna M. Varghese1, Martin H. Voss1, Rona Yaeger1, Marjorie G. Zauderer1, Nadeem R. Abu-Rustum1, Julio Garcia-Aguilar1, Bernard H. Bochner1, A.A. Hakimi1, William R. Jarnagin1, David R. Jones1, Daniela Molena1, Luc G. T. Morris1, Eric Rios-Doria1, Paul Russo1, Samuel Singer1, Vivian E. Strong1, Debyani Chakravarty1, Lora H. Ellenson1, Anuradha Gopalan1, Jorge S. Reis-Filho1, Britta Weigelt1, Marc Ladanyi1, Mithat Gonen1, Sohrab P. Shah1, Joan Massagué2, Jianjiong Gao1, Ahmet Zehir1, Michael F. Berger1, David B. Solit, Samuel F. Bakhoum1, Francisco Sanchez-Vega1, Nikolaus Schultz1 
30 Jun 2021-bioRxiv
TL;DR: The MSK-MET dataset as discussed by the authors is an integrated pan-cancer cohort of tumor genomic and clinical outcome data from more than 25,000 patients to identify associations between tumor genomic alterations and patterns of metastatic dissemination across 50 tumor types.
Abstract: Progression to metastatic disease remains the main cause of cancer death. Yet, the underlying genomic mechanisms driving metastasis remain largely unknown. Here, we present MSK-MET, an integrated pan-cancer cohort of tumor genomic and clinical outcome data from more than 25,000 patients. We analyzed this dataset to identify associations between tumor genomic alterations and patterns of metastatic dissemination across 50 tumor types. We found that chromosomal instability is strongly correlated with metastatic burden in some tumor types, including prostate adenocarcinoma, lung adenocarcinoma and HR-positive breast ductal carcinoma, but not in others, such as colorectal adenocarcinoma, pancreatic adenocarcinoma and high-grade serous ovarian cancer. We also identified specific somatic alterations associated with increased metastatic burden and specific routes of metastatic spread. Our data offer a unique resource for the investigation of the biological basis for metastatic spread and highlight the crucial role of chromosomal instability in cancer progression.

108 citations

Journal ArticleDOI
TL;DR: In this paper, the extent to which mutation profiling guides therapy selection in patients with advanced cancer was determined, and it was shown that mutation profiling is increasingly performed in patients who have advanced cancer.
Abstract: PURPOSETumor mutational profiling is increasingly performed in patients with advanced cancer. We determined the extent to which germline mutation profiling guides therapy selection in patients with...

61 citations

Posted ContentDOI
30 Oct 2021-medRxiv
TL;DR: In this article, a comparative genetic analyses analysis of 2,138 sarcomas representing 45 pathological entities was performed using targeted sequencing to characterize sub-specific somatic alterations in targetable pathways, rates of whole genome doubling, mutational signatures, and subtype-agnostic genomic clusters.
Abstract: The genetic, biologic, and clinical heterogeneity of sarcomas poses a challenge for the identification of therapeutic targets, clinical research, and advancing patient care. Because there are > 100 sarcoma subtypes, in-depth genetic studies have focused on one or a few subtypes. Herein, we report a comparative genetic analyses analysis of 2,138 sarcomas representing 45 pathological entities. This cohort was prospectively analyzed using targeted sequencing to characterize subtype-specific somatic alterations in targetable pathways, rates of whole genome doubling, mutational signatures, and subtype-agnostic genomic clusters. The most common alterations were in cell cycle control and TP53, receptor tyrosine kinases/PI3K/RAS, and epigenetic regulators. Subtype-specific associations included TERT amplification in intimal sarcoma and SWI/SNF alterations in uterine adenosarcoma. Tumor mutational burden, while low compared to other cancers, varied between and within subtypes. This resource will improve sarcoma models, motivate studies of subtype-specific alterations, and inform investigations of genetic factors and their correlations with treatment response.

1 citations


Cited by
More filters
Journal ArticleDOI
TL;DR: In this paper , age-specific risk estimates of cancers other than female breast and ovarian cancers associated with pathogenic variants (PVs) in BRCA1 and BRCa2 for effective cancer risk management were provided.
Abstract: To provide precise age-specific risk estimates of cancers other than female breast and ovarian cancers associated with pathogenic variants (PVs) in BRCA1 and BRCA2 for effective cancer risk management.We used data from 3,184 BRCA1 and 2,157 BRCA2 families in the Consortium of Investigators of Modifiers of BRCA1/2 to estimate age-specific relative (RR) and absolute risks for 22 first primary cancer types adjusting for family ascertainment.BRCA1 PVs were associated with risks of male breast (RR = 4.30; 95% CI, 1.09 to 16.96), pancreatic (RR = 2.36; 95% CI, 1.51 to 3.68), and stomach (RR = 2.17; 95% CI, 1.25 to 3.77) cancers. Associations with colorectal and gallbladder cancers were also suggested. BRCA2 PVs were associated with risks of male breast (RR = 44.0; 95% CI, 21.3 to 90.9), stomach (RR = 3.69; 95% CI, 2.40 to 5.67), pancreatic (RR = 3.34; 95% CI, 2.21 to 5.06), and prostate (RR = 2.22; 95% CI, 1.63 to 3.03) cancers. The stomach cancer RR was higher for females than males (6.89 v 2.76; P = .04). The absolute risks to age 80 years ranged from 0.4% for male breast cancer to approximately 2.5% for pancreatic cancer for BRCA1 carriers and from approximately 2.5% for pancreatic cancer to 27% for prostate cancer for BRCA2 carriers.In addition to female breast and ovarian cancers, BRCA1 and BRCA2 PVs are associated with increased risks of male breast, pancreatic, stomach, and prostate (only BRCA2 PVs) cancers, but not with the risks of other previously suggested cancers. The estimated age-specific risks will refine cancer risk management in men and women with BRCA1/2 PVs.

52 citations

Journal ArticleDOI
TL;DR: The ASCO provisional clinical opinion as mentioned in this paper addresses the appropriate use of tumor genomic testing in patients with metastatic or advanced solid tumors, and provides guidance on when and how to interpret the results for treatment selection, including the functional impact of targeted alteration and expected efficacy of genomic biomarker-linked options relative to other approved or investigational treatments.
Abstract: An ASCO provisional clinical opinion offers timely clinical direction to ASCO's membership following publication or presentation of potentially practice-changing data from major studies. This provisional clinical opinion addresses the appropriate use of tumor genomic testing in patients with metastatic or advanced solid tumors.An increasing number of therapies are approved to treat cancers harboring specific genomic biomarkers. However, there is a lack of clarity as to when tumor genomic sequencing should be ordered, what type of assays should be performed, and how to interpret the results for treatment selection.Patients with metastatic or advanced cancer should undergo genomic sequencing in a certified laboratory if the presence of one or more specific genomic alterations has regulatory approval as biomarkers to guide the use of or exclusion from certain treatments for their disease. Multigene panel-based assays should be used if more than one biomarker-linked therapy is approved for the patient's disease. Site-agnostic approvals for any cancer with a high tumor mutation burden, mismatch repair deficiency, or neurotrophic tyrosine receptor kinase (NTRK) fusions provide a rationale for genomic testing for all solid tumors. Multigene testing may also assist in treatment selection by identifying additional targets when there are few or no genotype-based therapy approvals for the patient's disease. For treatment planning, the clinician should consider the functional impact of the targeted alteration and expected efficacy of genomic biomarker-linked options relative to other approved or investigational treatments.Additional information is available at www.asco.org/assays-and-predictive-markers-guidelines.

51 citations

Journal ArticleDOI
Shuai Li, Valentina Silvestri, Goska Leslie, Timothy R. Rebbeck, Susan L. Neuhausen, John L. Hopper, Henriette Roed Nielsen, Andrew Lee, Xin Yang, Lesley McGuffog, Michael T. Parsons, Irene L. Andrulis, Norbert Arnold, Muriel Belotti, Åke Borg, Bruno Buecher, Saundra S. Buys, Sandrine M. Caputo, Wendy K. Chung, Chrystelle Colas, Sarah Colonna, Jackie Cook, Mary B. Daly, M. De La Hoya, Antoine De Pauw, Hélène Delhomelle, Jacqueline Eason, Christoph Engel, D. Gareth Evans, Ulrike Faust, Tanja Fehm, Florentia Fostira, George Fountzilas, Megan N. Frone, Vanesa García-Barberán, Pilar Garre, Marion Gauthier-Villars, Andrea Gehrig, Gord Glendon, David E. Goldgar, Lisa Golmard, Mark I. Greene, Eric Hahnen, Ute Hamann, Helen L. Hanson, Tiara Hassan, Julia Hentschel, Judit Horvath, Louise Izatt, Ramunas Janavicius, Yue Jiao, Esther M. John, Beth Y. Karlan, Sung-Woon Kim, Irene Konstantopoulou, Ava Kwong, Anthony Laugé, Jong Won Lee, Fabienne Lesueur, Noura Mebirouk, Alfons Meindl, Emmanuelle Mouret-Fourme, Hannah Musgrave, Joanne Ngeow Yuen Yie, Dieter Niederacher, Sue K. Park, Inge Søkilde Pedersen, Juliane Ramser, Susan J. Ramus, Johanna Rantala, Muhammad Usman Rashid, Florian Reichl, Julia Ritter, Andreas Rump, Marta Santamariña, Claire Saule, Gunnar Schmidt, Rita K. Schmutzler, Leigha Senter, Sabariah Shariff, Christian F. Singer, Melissa C. Southey, Dominique Stoppa-Lyonnet, Christian Sutter, Yen Y. Tan, Soo Hwang Teo, Mary Beth Terry, Mads Thomassen, Marc Tischkowitz, Amanda E. Toland, Diana Torres, Ana Vega, Sebastian Wagner, Shan Wang-Gohrke, Barbara Wappenschmidt, Bernhard H. F. Weber, Drakoulis Yannoukakos, Amanda B. Spurdle, Douglas F. Easton, Georgia Chenevix-Trench, Laura Ottini, Antonis C. Antoniou 
TL;DR: BRCA1 and BRCA2 PVs are associated with increased risks of male breast, pancreatic, stomach, and prostate cancers, but not with the risks of other previously suggested cancers.
Abstract: PURPOSE To provide precise age-specific risk estimates of cancers other than female breast and ovarian cancers associated with pathogenic variants (PVs) in BRCA1 and BRCA2 for effective cancer risk management. METHODS We used data from 3,184 BRCA1 and 2,157 BRCA2 families in the Consortium of Investigators of Modifiers of BRCA1/2 to estimate age-specific relative (RR) and absolute risks for 22 first primary cancer types adjusting for family ascertainment. RESULTS BRCA1 PVs were associated with risks of male breast (RR = 4.30; 95% CI, 1.09 to 16.96), pancreatic (RR = 2.36; 95% CI, 1.51 to 3.68), and stomach (RR = 2.17; 95% CI, 1.25 to 3.77) cancers. Associations with colorectal and gallbladder cancers were also suggested. BRCA2 PVs were associated with risks of male breast (RR = 44.0; 95% CI, 21.3 to 90.9), stomach (RR = 3.69; 95% CI, 2.40 to 5.67), pancreatic (RR = 3.34; 95% CI, 2.21 to 5.06), and prostate (RR = 2.22; 95% CI, 1.63 to 3.03) cancers. The stomach cancer RR was higher for females than males (6.89 v 2.76; P = .04). The absolute risks to age 80 years ranged from 0.4% for male breast cancer to approximately 2.5% for pancreatic cancer for BRCA1 carriers and from approximately 2.5% for pancreatic cancer to 27% for prostate cancer for BRCA2 carriers. CONCLUSION In addition to female breast and ovarian cancers, BRCA1 and BRCA2 PVs are associated with increased risks of male breast, pancreatic, stomach, and prostate (only BRCA2 PVs) cancers, but not with the risks of other previously suggested cancers. The estimated age-specific risks will refine cancer risk management in men and women with BRCA1/2 PVs.

41 citations

Journal ArticleDOI
TL;DR: Patients with metastatic or advanced cancer should undergo genomic sequencing in a certified laboratory if the presence of one or more specific genomic alterations has regulatory approval as biomarkers to guide the use of or exclusion from certain treatments for their disease.
Abstract: PURPOSE An ASCO provisional clinical opinion offers timely clinical direction to ASCO's membership following publication or presentation of potentially practice-changing data from major studies. This provisional clinical opinion addresses the appropriate use of tumor genomic testing in patients with metastatic or advanced solid tumors. CLINICAL CONTEXT An increasing number of therapies are approved to treat cancers harboring specific genomic biomarkers. However, there is a lack of clarity as to when tumor genomic sequencing should be ordered, what type of assays should be performed, and how to interpret the results for treatment selection. PROVISIONAL CLINICAL OPINION Patients with metastatic or advanced cancer should undergo genomic sequencing in a certified laboratory if the presence of one or more specific genomic alterations has regulatory approval as biomarkers to guide the use of or exclusion from certain treatments for their disease. Multigene panel-based assays should be used if more than one biomarker-linked therapy is approved for the patient's disease. Site-agnostic approvals for any cancer with a high tumor mutation burden, mismatch repair deficiency, or neurotrophic tyrosine receptor kinase (NTRK) fusions provide a rationale for genomic testing for all solid tumors. Multigene testing may also assist in treatment selection by identifying additional targets when there are few or no genotype-based therapy approvals for the patient's disease. For treatment planning, the clinician should consider the functional impact of the targeted alteration and expected efficacy of genomic biomarker-linked options relative to other approved or investigational treatments.Additional information is available at www.asco.org/assays-and-predictive-markers-guidelines.

40 citations