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4. Utility of Genomic Analysis In Circulating Tumor DNA from Patients with Carcinoma of Unknown Primary

Author

Kato, Shumei, Krishnamurthy, Nithya, Banks, Kimberly C, De, Pradip, Williams, Kirstin, Williams, Casey, Leyland-Jones, Brian, Lippman, Scott M, Lanman, Richard B, and Kurzrock, Razelle

Subjects
Genetics, Biotechnology, Human Genome, Clinical Research, Cancer, Good Health and Well Being, Adult, Aged, Aged, 80 and over, DNA, Neoplasm, Female, Genomics, Humans, Male, Middle Aged, Neoplasms, Unknown Primary, Young Adult, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

Carcinoma of unknown primary (CUP) is a rare and difficult-to-treat malignancy, the management of which might be improved by the identification of actionable driver mutations. We interrogated 54 to 70 genes in 442 patients with CUP using targeted clinical-grade, next-generation sequencing of circulating tumor DNA (ctDNA). Overall, 80% of patients exhibited ctDNA alterations; 66% (290/442) ≥1 characterized alteration(s), excluding variants of unknown significance. TP53-associated genes were most commonly altered [37.8% (167/442)], followed by genes involved in the MAPK pathway [31.2% (138/442)], PI3K signaling [18.1% (80/442)], and the cell-cycle machinery [10.4% (46/442)]. Among 290 patients harboring characterized alterations, distinct genomic profiles were observed in 87.9% (255/290) of CUP cases, with 99.7% (289/290) exhibiting potentially targetable alterations. An illustrative patient with dynamic changes in ctDNA content during therapy and a responder given a checkpoint inhibitor-based regimen because of a mismatch repair gene anomaly are presented. Our results demonstrate that ctDNA evaluation is feasible in CUP and that most patients harbor a unique somatic profile with pharmacologically actionable alterations, justifying the inclusion of noninvasive liquid biopsies in next-generation clinical trials. Cancer Res; 77(16); 4238-46. ©2017 AACR.

Published
2017

7. Figure 3 from: Williams KA, Steenkamp JC, Snyman LP (2023) Beyond Asilidae: The collecting effort of Dr Jason Londt as represented by non-Asilidae Diptera, Hemiptera and Mecoptera, housed in the KwaZulu-Natal Museum, South Africa. In: Dikow T, Williams K, Midgley J (Eds) Festschrift for Jason Gilbert Hayden Londt. African Invertebrates 64(2): 79-84. https://doi.org/10.3897/afrinvertebr.64.98587

Author

Williams, Kirstin A., primary, Steenkamp, Jacobus C., additional, and Snyman, Louwrens P., additional

Published
2023
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8. Figure 1 from: Williams KA, Steenkamp JC, Snyman LP (2023) Beyond Asilidae: The collecting effort of Dr Jason Londt as represented by non-Asilidae Diptera, Hemiptera and Mecoptera, housed in the KwaZulu-Natal Museum, South Africa. In: Dikow T, Williams K, Midgley J (Eds) Festschrift for Jason Gilbert Hayden Londt. African Invertebrates 64(2): 79-84. https://doi.org/10.3897/afrinvertebr.64.98587

Author

Williams, Kirstin A., primary, Steenkamp, Jacobus C., additional, and Snyman, Louwrens P., additional

Published
2023
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9. Figure 2 from: Williams KA, Steenkamp JC, Snyman LP (2023) Beyond Asilidae: The collecting effort of Dr Jason Londt as represented by non-Asilidae Diptera, Hemiptera and Mecoptera, housed in the KwaZulu-Natal Museum, South Africa. In: Dikow T, Williams K, Midgley J (Eds) Festschrift for Jason Gilbert Hayden Londt. African Invertebrates 64(2): 79-84. https://doi.org/10.3897/afrinvertebr.64.98587

Author

Williams, Kirstin A., primary, Steenkamp, Jacobus C., additional, and Snyman, Louwrens P., additional

Published
2023
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15. Beyond Asilidae: The collecting effort of Dr Jason Londt as represented by non-Asilidae Diptera, Hemiptera and Mecoptera, housed in the KwaZulu-Natal Museum, South Africa.

Author

Williams, Kirstin A., Steenkamp, Jacobus C., and Snyman, Louwrens P.

Subjects
*DIPTERA, *HISTORIC house museums, *NUMBERS of species, *VETERINARY microbiology
Abstract

The article presents the discussion on research focusing the taxonomy of Afrotropical Asilidae contributing to the taxonomy of Mecoptera and collected impressive numbers of other Diptera and Hemiptera. Topics include Jason Londt’s passion for entomology and collecting being clearly be seen in the number of specimens collected during the time at the KZN Museum; and adding specimens to the collection, which is a reflection of his unwavering dedication to dipterology.

Published
2023
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16. RET rearrangements are actionable alterations in breast cancer

Author

Paratala, Bhavna S., Chung, Jon H., Williams, Casey B., Yilmazel, Bahar, Petrosky, Whitney, Williams, Kirstin, Schrock, Alexa B., Gay, Laurie M., Lee, Ellen, Dolfi, Sonia C., Pham, Kien, Lin, Stephanie, Yao, Ming, Kulkarni, Atul, DiClemente, Frances, Liu, Chen, Rodriguez-Rodriguez, Lorna, Ganesan, Shridar, Ross, Jeffrey S., Ali, Siraj M., Leyland-Jones, Brian, and Hirshfield, Kim M.

Published
2018
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36. Abstract PS9-11: Health-related quality of life for margetuximab + chemotherapy vs. trastuzumab + chemotherapy in the phase 3 SOPHIA trial of patients with pretreated HER2+ metastatic breast cancer

Author

Cardoso, Fatima, primary, Cortes, Javier, additional, Gradishar, William, additional, Im, Seock-Ah, additional, Pegram, Mark D., additional, Rugo, Hope S., additional, Wright, Gail S., additional, De Laurentiis, Michelino, additional, Levy, Christelle, additional, Ferrero, Jean-Marc, additional, Mansi, Janine, additional, Oyola, Raul, additional, Ricci, Francesco, additional, Jakobsen, Erik H., additional, Uziely, Beatriz, additional, Egle, Daniel, additional, Giagounidis, Aristoteles, additional, Williams, Kirstin, additional, Hong, Shengyan, additional, Rock, Edwin, additional, and Curigliano, Giuseppe, additional

Published
2021
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39. Results of a phase Ib trial evaluating the safety and clinical activity of sapanisertib (TAK 228) in combination with serabelisib (TAK 117) and paclitaxel in patients with advanced ovarian, endometrial, or breast cancer.

Author

Williams, Casey B., primary, Williams, Kirstin Anne, additional, Krie, Amy K., additional, De, Pradip, additional, Dey, Nandini, additional, Leyland-Jones, Brian, additional, Starks, David, additional, and Rojas-Espaillat, Luis Alexander, additional

Published
2020
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40. Abstract 5147: Clinical benefit of molecularly-guided treatment strategies on progression free survival in patients with advanced gastrointestinal malignancies

Author

Buzard, Blake, primary, Gonser, Tyler, additional, Hinrichsen, Melissa, additional, Amallraja, Anu, additional, Williams, Kirstin, additional, De, Pradip, additional, Leyland-Jones, Brian, additional, Elsey, Rachel, additional, Meissner, Tobias, additional, and Williams, Casey, additional

Published
2019
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41. Abstract 3451: Testing signaling algorithm in platinum-resistant ovarian carcinomas: A simultaneous inhibition of RAS-RAF and cell-cycle pathways signals by trametinib with paclitaxel or ribociclib/abemaciclib

Author

Dey, Nandini, primary, Williams, Casey, additional, Williams, Kirstin, additional, Klein, Jessica, additional, Carlson, Jennifer H., additional, Starks, David, additional, Espaillat, Luis Rojas, additional, De, Pradip, additional, and Jones, Brian Leyland, additional

Published
2018
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45. Species identification of adult African blowflies (Diptera: Calliphoridae) of forensic importance

Author

Lutz, Lena, Williams, Kirstin A., Villet, Martin H., Ekanem, Mfon, Szpila, Krzysztof, Lutz, Lena, Williams, Kirstin A., Villet, Martin H., Ekanem, Mfon, and Szpila, Krzysztof

Abstract

Necrophagous blowflies can provide an excellent source of evidence for forensic entomologists and are also relevant to problems in public health, medicine, and animal health. However, access to useful information about these blowflies is constrained by the need to correctly identify the flies, and the poor availability of reliable, accessible identification tools is a serious obstacle to the development of forensic entomology in the majority of African countries. In response to this need, a high-quality key to the adults of all species of forensically relevant blowflies of Africa has been prepared, drawing on high-quality entomological materials and modern focus-stacking photomicroscopy. This new key can be easily applied by investigators inexperienced in the taxonomy of blowflies and is made available through a highly accessible online platform. Problematic diagnostic characters used in previous keys are discussed.

Published
2017

46. Nocturnal oviposition behavior of blowflies (Diptera: Calliphoridae) in the southern hemisphere (South Africa and Australia) and its forensic implications

Author

Williams, Kirstin A, Wallman, James F, Lessard, Bryan D, Kavazos, Christopher, Mazungula, D Nkosinathi, Villet, Martin, Williams, Kirstin A, Wallman, James F, Lessard, Bryan D, Kavazos, Christopher, Mazungula, D Nkosinathi, and Villet, Martin

Abstract

Published research has offered contradictory evidence of the occurrence of nocturnal oviposition by carrion-breeding blowflies, a behavior that can affect the interpretation of forensic estimates of a minimum post mortem interval (minPMI) by up to 12 hours, depending on latitude and season. The majority of published studies are from the northern hemisphere. Field experiments were conducted in South Africa and Australia that extend observations to species of the southern hemisphere. Various vertebrate carrion was exposed at night in summer under different lunar phases and/or artificial lighting, and in woodland and pasture areas. Three laboratory experiments were also conducted. No nocturnal oviposition occurred outdoors in Berry, Australia, but Lucilia cuprina, Lucilia sericata and Chrysomya megacephala laid eggs outdoors at night in Grahamstown and Durban, South Africa. In laboratory experiments L. sericata, L. cuprina, Chrysomya chloropyga and Chrysomya putoria laid eggs and Calliphora augur deposited larvae under nocturnal conditions. Chrysomya albiceps and C. chloropyga laid eggs in darkness with increasing likelihood as ambient temperature increased. This study shows that nocturnal ovi/larviposition by carrion-breeding blowflies is possible in both South Africa and Australia. The forensic issue is therefore not whether nocturnal oviposition occurs, but rather whether the conditions of a particular case are more or less conducive to it. Circadian rhythms and physiological thresholds (particularly temperature and humidity) appear to act individually and in conjunction to stimulate or inhibit nocturnal laying. The significance of carcass size, freezing and handling of carcasses and comprehensive quantification for experimental design is discussed, and recommendations are made for future laboratory and case scene experiments.

Published
2017

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