ORCID Profile
0000-0002-6070-2413
Current Organisation
Memorial Sloan Kettering Cancer Center
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Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22480629
Abstract: Supplemental Figure 3. Comparison of overall and recurrence-free survival in TP53-wild type and TP53-mutant IMAs
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22535389
Abstract: Comprehensive OncoPrint of nine patients with paired pre- and post-treatment tissue sequencing showing acquired alterations in the post-treatment tumor.
Publisher: Springer Science and Business Media LLC
Date: 15-03-2021
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22480626
Abstract: Supplemental Figure 4. Comparison of overall and recurrence-free survival in CDKN2A-wild type and CDKN2A-mutant IMAs.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22480620.V1
Abstract: Supplemental Methods 2
Publisher: American Association for Cancer Research (AACR)
Date: 17-07-2001
DOI: 10.1158/1078-0432.CCR-21-0423
Abstract: Invasive mucinous adenocarcinoma (IMA) is a unique subtype of lung adenocarcinoma, characterized genomically by frequent KRAS mutations or specific gene fusions, most commonly involving NRG1. Comprehensive analysis of a large series of IMAs using broad DNA- and RNA-sequencing methods is still lacking, and it remains unclear whether molecular subtypes of IMA differ clinicopathologically. A total of 200 IMAs were analyzed by 410-gene DNA next-generation sequencing (MSK-IMPACT n = 136) or hotspot 8-oncogene genotyping (n = 64). Driver-negative cases were further analyzed by 62-gene RNA sequencing (MSK-Fusion) and those lacking fusions were further tested by whole-exome sequencing and whole-transcriptome sequencing (WTS). Combined MSK-IMPACT and MSK-Fusion testing identified mutually exclusive driver alterations in 96% of IMAs, including KRAS mutations (76%), NRG1 fusions (7%), ERBB2 alterations (6%), and other less common events. In addition, WTS identified a novel NRG2 fusion (F11R–NRG2). Overall, targetable gene fusions were identified in 51% of KRAS wild-type IMAs, leading to durable responses to targeted therapy in some patients. Compared with KRAS-mutant IMAs, NRG1-rearranged tumors exhibited several more aggressive characteristics, including worse recurrence-free survival (P & 0.0001). This is the largest molecular study of IMAs to date, where we demonstrate the presence of a major oncogenic driver in nearly all cases. This study is the first to document more aggressive characteristics of NRG1-rearranged IMAs, ERBB2 as the third most common alteration, and a novel NRG2 fusion in these tumors. Comprehensive molecular testing of KRAS wild-type IMAs that includes fusion testing is essential, given the high prevalence of alterations with established and investigational targeted therapies in this subset.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22480623
Abstract: Supplemental Methods 1
Publisher: American Society of Clinical Oncology (ASCO)
Date: 11-2021
DOI: 10.1200/PO.21.00055
Abstract: Low-grade serous carcinoma (LGSC) is a rare type of ovarian cancer, which commonly arises from serous borderline tumor (SBT) and is characterized by frequent activating mutations in the mitogen-activated protein kinase pathway, including BRAF. The BRAF V600E mutation is associated with improved prognosis in SBT and LGSC, and responses to BRAF inhibitor therapy have been reported. We sought to characterize the clinicopathologic and molecular features of BRAF-driven tubo-ovarian and primary peritoneal serous tumors. Retrospective analysis of our institutional cohort of SBTs (n = 22), LGSCs (n = 119) and high-grade serous carcinomas (HGSCs, n = 1,290) subjected to targeted massively parallel sequencing was performed to identify cases with BRAF genetic alterations. Putative BRAF rearrangements were confirmed using targeted RNA sequencing and/or fluorescence in situ hybridization (FISH). BRAF V600E oncoprotein expression was assessed by immunohistochemistry on selected cases. BRAF somatic genetic alterations were identified in 29 of 1,431 (2%) serous tumors and included mutations (n = 24), gene rearrangements (n = 3), and lification (n = 2). BRAF mutations were more frequent in SBTs (7 of 22 32%) compared with LGSCs (11 of 119 9%, P = .009) and HGSCs (6 of 1,290 0.5% P .0001, SBT/LGSC v HGSC). The BRAF V600E hotspot mutation was most common (n = 16) however, other BRAF driver mutations were also detected (n = 8). BRAF mutations were often clonal or truncal in SBTs and LGSCs, but subclonal in most HGSCs. Pathogenic BRAF gene fusions were identified in LGSCs (n = 2) and HGSC (n = 1) and involved distinct fusion partners ( AGK, MKRN1, and AGAP3). Three patients with BRAF-mutant LGSC were treated with targeted mitogen-activated protein kinase inhibitors, one of whom was maintained on therapy for over 3 years with clinical benefit. Recognition of BRAF alterations beyond V600E mutation in LGSC may have clinical implications for appropriate targeted therapy selection.
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22535395.V1
Abstract: PFS of (A) neratinib plus fulvestrant combination cohort and (B) neratinib monotherapy cohort. CI, confidence interval PFS, progression-free survival.
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22535398.V1
Abstract: Supplementary data
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22480620
Abstract: Supplemental Methods 2
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22480629.V1
Abstract: Supplemental Figure 3. Comparison of overall and recurrence-free survival in TP53-wild type and TP53-mutant IMAs
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22480626.V1
Abstract: Supplemental Figure 4. Comparison of overall and recurrence-free survival in CDKN2A-wild type and CDKN2A-mutant IMAs.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22480632.V1
Abstract: Supplemental Figure 2. Detailed graphical visualizations of the F11R-NRG2 fusion.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22480617.V1
Abstract: Supplemental Tables 1-11
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.C.6530487.V1
Abstract: AbstractPurpose: Invasive mucinous adenocarcinoma (IMA) is a unique subtype of lung adenocarcinoma, characterized genomically by frequent i KRAS /i mutations or specific gene fusions, most commonly involving i NRG1 /i . Comprehensive analysis of a large series of IMAs using broad DNA- and RNA-sequencing methods is still lacking, and it remains unclear whether molecular subtypes of IMA differ clinicopathologically. Experimental Design: A total of 200 IMAs were analyzed by 410-gene DNA next-generation sequencing (MSK-IMPACT i n /i = 136) or hotspot 8-oncogene genotyping ( i n /i = 64). Driver-negative cases were further analyzed by 62-gene RNA sequencing (MSK-Fusion) and those lacking fusions were further tested by whole-exome sequencing and whole-transcriptome sequencing (WTS). Results: Combined MSK-IMPACT and MSK-Fusion testing identified mutually exclusive driver alterations in 96% of IMAs, including i KRAS /i mutations (76%), i NRG1 /i fusions (7%), i ERBB2 /i alterations (6%), and other less common events. In addition, WTS identified a novel i NRG2 /i fusion ( i F11R /i – i NRG2 /i ). Overall, targetable gene fusions were identified in 51% of i KRAS /i wild-type IMAs, leading to durable responses to targeted therapy in some patients. Compared with i KRAS /i -mutant IMAs, i NRG1 /i -rearranged tumors exhibited several more aggressive characteristics, including worse recurrence-free survival ( i P /i 0.0001). Conclusions: This is the largest molecular study of IMAs to date, where we demonstrate the presence of a major oncogenic driver in nearly all cases. This study is the first to document more aggressive characteristics of i NRG1 /i -rearranged IMAs, i ERBB2 /i as the third most common alteration, and a novel i NRG2 /i fusion in these tumors. Comprehensive molecular testing of i KRAS /i wild-type IMAs that includes fusion testing is essential, given the high prevalence of alterations with established and investigational targeted therapies in this subset. /
Publisher: American Association for Cancer Research (AACR)
Date: 02-2020
DOI: 10.1158/2159-8290.CD-19-0966
Abstract: HER2 mutations define a targetable breast cancer subset, although sensitivity to irreversible HER kinase inhibition appears to be modified by the presence of concurrent activating genomic events in the pathway. These findings have implications for potential future combinatorial approaches and broader therapeutic development for this genomically defined subset of breast cancer. This article is highlighted in the In This Issue feature, p. 161
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22535398
Abstract: Supplementary data
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2014
DOI: 10.1158/2159-8290.22535395
Abstract: PFS of (A) neratinib plus fulvestrant combination cohort and (B) neratinib monotherapy cohort. CI, confidence interval PFS, progression-free survival.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22480617
Abstract: Supplemental Tables 1-11
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22480632
Abstract: Supplemental Figure 2. Detailed graphical visualizations of the F11R-NRG2 fusion.
Publisher: Springer Science and Business Media LLC
Date: 31-01-2018
DOI: 10.1038/NATURE25475
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22535392.V1
Abstract: Overall sequencing CONSORT diagram. Flow diagram of study patients and analyzed biospecimens processed through and selected for central sequencing using MSK-IMPACT and Guardant360. cfDNA, cell-free DNA FFPE, formalin-fixed paraffin-embedded MSK-IMPACT, Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets QC, quality control.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22480635
Abstract: Supplemental Figure 1. Consort diagram summarizing the molecular workflow of cases.
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22535392
Abstract: Overall sequencing CONSORT diagram. Flow diagram of study patients and analyzed biospecimens processed through and selected for central sequencing using MSK-IMPACT and Guardant360. cfDNA, cell-free DNA FFPE, formalin-fixed paraffin-embedded MSK-IMPACT, Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets QC, quality control.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22480623.V1
Abstract: Supplemental Methods 1
Publisher: Springer Science and Business Media LLC
Date: 23-03-2021
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2022
DOI: 10.1158/1078-0432.C.6530487
Abstract: AbstractPurpose: Invasive mucinous adenocarcinoma (IMA) is a unique subtype of lung adenocarcinoma, characterized genomically by frequent i KRAS /i mutations or specific gene fusions, most commonly involving i NRG1 /i . Comprehensive analysis of a large series of IMAs using broad DNA- and RNA-sequencing methods is still lacking, and it remains unclear whether molecular subtypes of IMA differ clinicopathologically. Experimental Design: A total of 200 IMAs were analyzed by 410-gene DNA next-generation sequencing (MSK-IMPACT i n /i = 136) or hotspot 8-oncogene genotyping ( i n /i = 64). Driver-negative cases were further analyzed by 62-gene RNA sequencing (MSK-Fusion) and those lacking fusions were further tested by whole-exome sequencing and whole-transcriptome sequencing (WTS). Results: Combined MSK-IMPACT and MSK-Fusion testing identified mutually exclusive driver alterations in 96% of IMAs, including i KRAS /i mutations (76%), i NRG1 /i fusions (7%), i ERBB2 /i alterations (6%), and other less common events. In addition, WTS identified a novel i NRG2 /i fusion ( i F11R /i – i NRG2 /i ). Overall, targetable gene fusions were identified in 51% of i KRAS /i wild-type IMAs, leading to durable responses to targeted therapy in some patients. Compared with i KRAS /i -mutant IMAs, i NRG1 /i -rearranged tumors exhibited several more aggressive characteristics, including worse recurrence-free survival ( i P /i 0.0001). Conclusions: This is the largest molecular study of IMAs to date, where we demonstrate the presence of a major oncogenic driver in nearly all cases. This study is the first to document more aggressive characteristics of i NRG1 /i -rearranged IMAs, i ERBB2 /i as the third most common alteration, and a novel i NRG2 /i fusion in these tumors. Comprehensive molecular testing of i KRAS /i wild-type IMAs that includes fusion testing is essential, given the high prevalence of alterations with established and investigational targeted therapies in this subset. /
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.C.6547849.V1
Abstract: Abstract i HER2 /i mutations define a subset of metastatic breast cancers with a unique mechanism of oncogenic addiction to HER2 signaling. We explored activity of the irreversible pan-HER kinase inhibitor neratinib, alone or with fulvestrant, in 81 patients with i HER2 /i -mutant metastatic breast cancer. Overall response rate was similar with or without estrogen receptor (ER) blockade. By comparison, progression-free survival and duration of response appeared longer in ER sup + /sup patients receiving combination therapy, although the study was not designed for direct comparison. Preexistent concurrent activating i HER2 /i or i HER3 /i alterations were associated with poor treatment outcome. Similarly, acquisition of multiple i HER2 /i -activating events, as well as gatekeeper alterations, were observed at disease progression in a high proportion of patients deriving clinical benefit from neratinib. Collectively, these data define i HER2 /i mutations as a therapeutic target in breast cancer and suggest that coexistence of additional HER signaling alterations may promote both i de novo /i and acquired resistance to neratinib. Significance: i HER2 /i mutations define a targetable breast cancer subset, although sensitivity to irreversible HER kinase inhibition appears to be modified by the presence of concurrent activating genomic events in the pathway. These findings have implications for potential future combinatorial approaches and broader therapeutic development for this genomically defined subset of breast cancer. i This article is highlighted in the In This Issue feature, p. 161 /i /
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22480635.V1
Abstract: Supplemental Figure 1. Consort diagram summarizing the molecular workflow of cases.
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22535389.V1
Abstract: Comprehensive OncoPrint of nine patients with paired pre- and post-treatment tissue sequencing showing acquired alterations in the post-treatment tumor.
Location: United States of America
No related grants have been discovered for Alison Schram.