Allelic Ratio of <i>KRAS</i> Mutations in Pancreatic Cancer

Lennerz, Jochen K.

doi:10.1634/theoncologist.2014-0408

Cited by 41 publications

(34 citation statements)

References 10 publications

(20 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We therefore turned to two cell lines isolated by Ying and colleagues from a doxycycline (dox)-inducible Kras G12D pancreatic ductal adenocarcinoma (PDAC) mouse model (Ying et al, 2012). KRAS is mutated in 90% of human PDACs and has been implicated as a driver of disease progression (Lennerz and Stenzinger, 2015). Consistent with these previous reports, Ying et al's cell lines, called iKras-1 and iKras-2, are dependent on dox for tumorigenicity in the mouse.…”

Section: Glycocalyx Height Increases Upon Epithelial To Mesenchymal Tsupporting

confidence: 59%

Quantitative Super-Resolution Microscopy of the Mammalian Glycocalyx

et al. 2019

View full text Add to dashboard Cite

The mammalian glycocalyx is a heavily glycosylated extramembrane compartment found on nearly every cell. Despite its relevance in both health and disease, studies of the glycocalyx remain hampered by a paucity of methods to spatially classify its components. We combine metabolic labeling, bioorthogonal chemistry, and super-resolution localization microscopy to image two constituents of cell-surface glycans, N-acetylgalactosamine (GalNAc) and sialic acid, with 10-20 nm precision in 2D and 3D. This approach enables two measurements: glycocalyx height and the distribution of individual sugars distal from the membrane. These measurements show that the glycocalyx exhibits nanoscale architecture, on both cell lines and primary human tumor cells. Additionally, we observe enhanced glycocalyx height in response to epithelial-tomesenchymal transition and to oncogenic KRAS activation. In the latter case, we trace increased height to an effector gene, GALNT7. These data highlight the power of advanced imaging methods to provide molecular and functional insights into glycocalyx biology.

show abstract

Section: Glycocalyx Height Increases Upon Epithelial To Mesenchymal Tsupporting

confidence: 59%

Quantitative Super-Resolution Microscopy of the Mammalian Glycocalyx

et al. 2019

View full text Add to dashboard Cite

show abstract

“…The hot-spot mutations in KRAS occur mainly at positions 12, 13, and 61 (28). In human cancers, KRAS mutations have been identified in approximately 90% of pancreatic ductal adenocarcinoma (PDAC) (37), and 33% in colorectal cancer (COSMIC database, http://cancer.sanger.ac.uk/cosmic). In this study, we detected and isolated TCR from CD4 + TILs targeting KRAS G12V .…”

Section: Discussionmentioning

confidence: 99%

Enhanced detection of neoantigen-reactive T cells targeting unique and shared oncogenes for personalized cancer immunotherapy

et al. 2018

View full text Add to dashboard Cite

“…In addition, the impact on PDAC biology may vary with the corrected tumor-specific allelic ratio (equal to allelic ratio divided by cellularity) and dosage of mutated KRAS. Recent reports have noted a trend for PDAC with a corrected allelic ratio of ≥10% to be associated with shorter OS (18). Additional genetic alterations in tumor suppressor genes such as cyclindependent kinase inhibitor 2A (CDKN2A) and TP53 lead to unrestricted cell growth and loss of apoptosis and growth arrest (19).…”

Section: Original Articlementioning

confidence: 99%

A KRAS wild type mutational status confers a survival advantage in pancreatic ductal adenocarcinoma

Windon¹,

Loaiza‐Bonilla²,

Jensen³

et al. 2018

J. Gastrointest. Oncol.

View full text Add to dashboard Cite

Similar to previously reported studies, PDAC with a wild type mutational profile has a better prognosis with a longer OS. This improved prognosis is independent of the protocol utilized in therapy for these patients. Our findings suggest that future clinical trials in pancreatic cancer should take into consideration the presence of mutations in their pre-planned analysis when assessing the efficacy of a novel therapeutic approach. This may be a crucial factor in trial concepts and outcomes.

show abstract

Allelic Ratio of KRAS Mutations in Pancreatic Cancer

Abstract: KRAS is not simply mutated or wild type in pancreatic ductal adenocarcinoma (PDAC); actually, it has never been. More than 90% of PDACs carry mutated KRAS alleles; however, the impact on PDAC biology may vary with the tumor‐specific allelic ratio and dosage of mutated KRAS.

Cited by 41 publications

References 10 publications

Quantitative Super-Resolution Microscopy of the Mammalian Glycocalyx

Quantitative Super-Resolution Microscopy of the Mammalian Glycocalyx

Enhanced detection of neoantigen-reactive T cells targeting unique and shared oncogenes for personalized cancer immunotherapy

A KRAS wild type mutational status confers a survival advantage in pancreatic ductal adenocarcinoma

Contact Info

Product

Resources

About