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Genomic Applications in Colorectal and Pancreatic Tumors

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Genomic Applications in Pathology

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Abstract

Colorectal cancer is one of the most common tumors in the Western world. Prior groundbreaking findings based on meticulous single gene analysis of colorectal tumors elucidated the progression from adenoma to invasive carcinoma in a multistep process driven by the accumulation of mutations in tumor suppressor genes (APC, p53, SMAD4) and oncogenes (KRAS). More recent high-throughput molecular genomic techniques confirmed the multistep model in the majority of sporadic colorectal cancers whereas smaller subgroup develop via different route, mostly initiated by a mutation in the BRAF oncogene, that results in oncogene-induced senescence (OIS) and the development of the gene methylator phenotype CIMP (CpG island methylator phenotype). Next-generation sequencing enables a more robust molecular classification of colorectal cancer, as well as pancreatic cancer. As a better understanding of the genetic alterations in pancreatic cancer emerges, it is becoming clear that a new molecular-based classification is possible. This classification would complement the morphologic classification system that has been developed and tested and integrates morphology and molecular findings into a cohesive system with prognostic and therapeutic implications.

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Conflict of Interest

Ralph Hruban receives royalty payments from Myriad Genetics for the PALB2 invention.

Andreas Jung is member of Advisory Boards for AMGEN and Merck Serono and received honoraria for presentations.

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Authors and Affiliations

  1. Pathologisches Institut, Ludwig-Maximilians Universität München, Munich, Germany

    Andreas Jung

  2. Departments of Pathology and Oncology, Johns Hopkins University, Baltimore, MD, USA

    Ralph Hruban

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  1. Andreas Jung
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Editor information

Editors and Affiliations

  1. Departments of Pathology, Oncology and Urology, Johns Hopkins University, Baltimore, Maryland, USA

    George Jabboure Netto

  2. Department of Pathology, Stanford University School of Medicine, Stanford, California, USA

    Iris Schrijver

Glossary

5-FU

5-Fluorouracil

CIMP

CpG island methylator phenotype

CIMP-H

High-grade CIMP

CIMP-L

Low-grade CIMP

ECM

Extracellular matrix

EGFR

Epidermal growth factor

EMT

Epithelio-mesenchymal transition

GEM

Genetically engineered mouse

Her2

EGFR 2

MLH1

MUT L homologue 1

MSH

MUT S homologue

TERT

Telomerase RT component

INK4a

Inhibitor of kinase 4

LEF-1

Lymphocyte enhancing factor-1

MGMT

O6-Methyl guanosine methyl transferase

miRNA

micro RNA

MMP

Matrix metalloproteinase 7

MSI-H

High-grade microsatellite instability

MT-MMP

Membrane-type MMP

ncRNA

Noncoding RNA

OIS

Oncogene-induced senescence

PMS

Postmitotic segregation

POL E

DNA polymerase ε

TCF

T-cell factor

uPA

Urokinase plasminogen activator

uPAR

uPA receptor

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Jung, A., Hruban, R. (2015). Genomic Applications in Colorectal and Pancreatic Tumors. In: Netto, G., Schrijver, I. (eds) Genomic Applications in Pathology. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0727-4_25

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