Comprehensive pan-cancer genomic landscape of KRAS altered cancers and real-world outcomes in solid tumors

Abstract Recent clinical development of KRAS inhibitors has heightened interest in the genomic landscape of KRAS-altered cancers. We performed a pan-cancer analysis of KRAS-altered samples from 426,706 adult patients with solid or hematologic malignancies using comprehensive genomic profiling; addit...
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Autor*in:	Jessica K. Lee [verfasserIn] Smruthy Sivakumar [verfasserIn] Alexa B. Schrock [verfasserIn] Russell Madison [verfasserIn] David Fabrizio [verfasserIn] Ole Gjoerup [verfasserIn] Jeffrey S. Ross [verfasserIn] Garrett M. Frampton [verfasserIn] Pavel Napalkov [verfasserIn] Meagan Montesion [verfasserIn] Jennifer L. Schutzman [verfasserIn] Xin Ye [verfasserIn] Priti S. Hegde [verfasserIn] Misako Nagasaka [verfasserIn] Geoffrey R. Oxnard [verfasserIn] Ethan S. Sokol [verfasserIn] Sai-Hong Ignatius Ou [verfasserIn] Zhen Shi [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Übergeordnetes Werk:	In: npj Precision Oncology - Nature Portfolio, 2017, 6(2022), 1, Seite 14
Übergeordnetes Werk:	volume:6 ; year:2022 ; number:1 ; pages:14

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1038/s41698-022-00334-z

Katalog-ID:	DOAJ085744298

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allfieldsSound	10.1038/s41698-022-00334-z doi (DE-627)DOAJ085744298 (DE-599)DOAJ127f5104a768437896be06715f4fd5c4 DE-627 ger DE-627 rakwb eng RC254-282 Jessica K. Lee verfasserin aut Comprehensive pan-cancer genomic landscape of KRAS altered cancers and real-world outcomes in solid tumors 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Recent clinical development of KRAS inhibitors has heightened interest in the genomic landscape of KRAS-altered cancers. We performed a pan-cancer analysis of KRAS-altered samples from 426,706 adult patients with solid or hematologic malignancies using comprehensive genomic profiling; additional analyses included 62,369 liquid biopsy and 7241 pediatric samples. 23% of adult pan-cancer samples had KRAS alterations; 88% were mutations, most commonly G12D/G12V/G12C/G13D/G12R, and prevalence was similar in liquid biopsies. Co-alteration landscapes were largely similar across KRAS mutations but distinct from KRAS wild-type, though differences were observed in some tumor types for tumor mutational burden, PD-L1 expression, microsatellite instability, and other mutational signatures. Prognosis of KRAS-mutant versus other genomic cohorts of lung, pancreatic, and colorectal cancer were assessed using a real-world clinicogenomic database. As specific KRAS inhibitors and combination therapeutic strategies are being developed, genomic profiling to understand co-alterations and other biomarkers that may modulate response to targeted or immunotherapies will be imperative. Neoplasms. Tumors. Oncology. Including cancer and carcinogens Smruthy Sivakumar verfasserin aut Alexa B. Schrock verfasserin aut Russell Madison verfasserin aut David Fabrizio verfasserin aut Ole Gjoerup verfasserin aut Jeffrey S. Ross verfasserin aut Garrett M. Frampton verfasserin aut Pavel Napalkov verfasserin aut Meagan Montesion verfasserin aut Jennifer L. Schutzman verfasserin aut Xin Ye verfasserin aut Priti S. Hegde verfasserin aut Misako Nagasaka verfasserin aut Geoffrey R. Oxnard verfasserin aut Ethan S. Sokol verfasserin aut Sai-Hong Ignatius Ou verfasserin aut Zhen Shi verfasserin aut In npj Precision Oncology Nature Portfolio, 2017 6(2022), 1, Seite 14 (DE-627)884384454 (DE-600)2891458-2 2397768X nnns volume:6 year:2022 number:1 pages:14 https://doi.org/10.1038/s41698-022-00334-z kostenfrei https://doaj.org/article/127f5104a768437896be06715f4fd5c4 kostenfrei https://doi.org/10.1038/s41698-022-00334-z kostenfrei https://doaj.org/toc/2397-768X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 6 2022 1 14
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author	Jessica K. Lee
spellingShingle	Jessica K. Lee misc RC254-282 misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens Comprehensive pan-cancer genomic landscape of KRAS altered cancers and real-world outcomes in solid tumors
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topic_title	RC254-282 Comprehensive pan-cancer genomic landscape of KRAS altered cancers and real-world outcomes in solid tumors
topic	misc RC254-282 misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
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title	Comprehensive pan-cancer genomic landscape of KRAS altered cancers and real-world outcomes in solid tumors
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title_full	Comprehensive pan-cancer genomic landscape of KRAS altered cancers and real-world outcomes in solid tumors
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title_sort	comprehensive pan-cancer genomic landscape of kras altered cancers and real-world outcomes in solid tumors
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title_auth	Comprehensive pan-cancer genomic landscape of KRAS altered cancers and real-world outcomes in solid tumors
abstract	Abstract Recent clinical development of KRAS inhibitors has heightened interest in the genomic landscape of KRAS-altered cancers. We performed a pan-cancer analysis of KRAS-altered samples from 426,706 adult patients with solid or hematologic malignancies using comprehensive genomic profiling; additional analyses included 62,369 liquid biopsy and 7241 pediatric samples. 23% of adult pan-cancer samples had KRAS alterations; 88% were mutations, most commonly G12D/G12V/G12C/G13D/G12R, and prevalence was similar in liquid biopsies. Co-alteration landscapes were largely similar across KRAS mutations but distinct from KRAS wild-type, though differences were observed in some tumor types for tumor mutational burden, PD-L1 expression, microsatellite instability, and other mutational signatures. Prognosis of KRAS-mutant versus other genomic cohorts of lung, pancreatic, and colorectal cancer were assessed using a real-world clinicogenomic database. As specific KRAS inhibitors and combination therapeutic strategies are being developed, genomic profiling to understand co-alterations and other biomarkers that may modulate response to targeted or immunotherapies will be imperative.
abstractGer	Abstract Recent clinical development of KRAS inhibitors has heightened interest in the genomic landscape of KRAS-altered cancers. We performed a pan-cancer analysis of KRAS-altered samples from 426,706 adult patients with solid or hematologic malignancies using comprehensive genomic profiling; additional analyses included 62,369 liquid biopsy and 7241 pediatric samples. 23% of adult pan-cancer samples had KRAS alterations; 88% were mutations, most commonly G12D/G12V/G12C/G13D/G12R, and prevalence was similar in liquid biopsies. Co-alteration landscapes were largely similar across KRAS mutations but distinct from KRAS wild-type, though differences were observed in some tumor types for tumor mutational burden, PD-L1 expression, microsatellite instability, and other mutational signatures. Prognosis of KRAS-mutant versus other genomic cohorts of lung, pancreatic, and colorectal cancer were assessed using a real-world clinicogenomic database. As specific KRAS inhibitors and combination therapeutic strategies are being developed, genomic profiling to understand co-alterations and other biomarkers that may modulate response to targeted or immunotherapies will be imperative.
abstract_unstemmed	Abstract Recent clinical development of KRAS inhibitors has heightened interest in the genomic landscape of KRAS-altered cancers. We performed a pan-cancer analysis of KRAS-altered samples from 426,706 adult patients with solid or hematologic malignancies using comprehensive genomic profiling; additional analyses included 62,369 liquid biopsy and 7241 pediatric samples. 23% of adult pan-cancer samples had KRAS alterations; 88% were mutations, most commonly G12D/G12V/G12C/G13D/G12R, and prevalence was similar in liquid biopsies. Co-alteration landscapes were largely similar across KRAS mutations but distinct from KRAS wild-type, though differences were observed in some tumor types for tumor mutational burden, PD-L1 expression, microsatellite instability, and other mutational signatures. Prognosis of KRAS-mutant versus other genomic cohorts of lung, pancreatic, and colorectal cancer were assessed using a real-world clinicogenomic database. As specific KRAS inhibitors and combination therapeutic strategies are being developed, genomic profiling to understand co-alterations and other biomarkers that may modulate response to targeted or immunotherapies will be imperative.
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title_short	Comprehensive pan-cancer genomic landscape of KRAS altered cancers and real-world outcomes in solid tumors
url	https://doi.org/10.1038/s41698-022-00334-z https://doaj.org/article/127f5104a768437896be06715f4fd5c4 https://doaj.org/toc/2397-768X
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up_date	2024-07-03T16:35:52.037Z
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Comprehensive pan-cancer genomic landscape of KRAS altered cancers and real-world outcomes in solid tumors

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