The Johns Hopkins University

Faster Better Media LLC

Scott E Kern

Bert Vogelstein

Kenneth W Kinzler

Nickolas Papadopoulos

Stephan A Hahn

Jonathan R Brody

Victor E Velculescu

Ralph Hruban

Sian Jones

D Williams Parsons

Rebecca J Leary

Giovanni Parmigiani

Michael Goggins

Xiaosong Zhang

Rachel Karchin

Manuel Medina Hidalgo

Leigh Zawel

James R Eshleman

Tomas Hucl

Gloria Su

Eike Gallmeier

Jia Le Dai

Alison Klein

Philipp Angenendt

Donald William Parsons

Jimmy Chang-Ho Lin

The present invention provides a method for detecting mutations in the PALB2 gene in pancreatic cancer patients and in individuals having a family history of pancreatic cancer. Methods are also provided for diagnosing a predisposition to pancreatic cancer, for predicting a patient's response to pancreatic cancer therapies, and for treating pancreatic cancer, based on presence of a PALB2 mutation or abberant PALB2 gene expression in a patient.

Diagnostic method using PALB2

Provided herein are compositions and methods for assaying the deleteriousness of putative loss-of-function mutations, especially in genes known to be or suspected of being tumor-suppressor genes. The invention includes syngeneic variance libraries and methods of construction and use of syngeneic variance libraries.

Functional assay for identification of loss-of-function mutations in genes

A series of low molarity conductive media based on non-buffering univalent cations, such as sodium chloride-sodium acetate (SCA), sodium boric acid (SB), lithium boric acid, and lithium acetate mitigate the 'runaway' positive feedback heating loop produced by conventional media containing biological amine buffers and permit improved DNA electrophoresis under the conditions of low salt concentration. These media serve well in ultra-fast DNA electrophoresis and in high-resolution separations of RNA and DNA fragments.

Conductive media for electrophoresis

A previously unknown histone acetylase inhibitor, 6-(1,3-Dioxo-1H, 3H-benzo&lsqb;de&rsqb;isoquinolin-2-yl)-hexanoic acid hydroxyamide, termed &ldquo;scriptaid,&rdquo; can be used to enhance transcription. Scriptaid can be added to transactivation assays, or can be used, for example, to increase production of therapeutic polypeptides in vitro and in vivo.

Methods and reagents for facilitating transcription

Two human Smad proteins (Smad3 and Smad4) specifically recognize an identical 8 bp palindromic sequence (GTCTAGAC) (SEQ ID NO: 1). Tandem repeats of this palindrome confer striking TGF-.beta. responsiveness to a minimal promoter. This responsiveness is abrogated by targeted deletion of the cellular Smad4 gene. DNA molecules comprising the 8 bp palindromic sequence can be used in assays for drug screening and diagnostically.

Human Smad3 and Smad4 are sequence-specific transcription activators

Polynucleotide and polypeptide sequences encoding a novel tumor suppressor gene, DPC4, are provided. Also included is a method for detecting a cell proliferative disorder associated with DPC4. DPC4 is a marker which can be used diagnostically, prognostically and therapeutically over the course of disorders associated with DPC4.

Tumor suppressor gene, DPC4

DPC4 polypeptide

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Hunt Valley, MD, United States of America

Scott E Kern