Deepankar Chakroborty

Genentech · Department of Molecular Oncology

Cancer tissues harbor thousands of mutations, and a given oncogene may be mutated at hundreds of sites. Yet, only a few of these mutations have been functionally tested. Here, we describe an unbiased platform for the functional characterization of thousands of variants of a single receptor tyrosine kinase (RTK) gene in a single assay. Our in vitro...

Background Prognostic markers specific to a particular cancer type can assist in the evaluation of survival probability of patients and help clinicians to assess the available treatment modalities. Methods Gene expression data was analyzed from three independent colon cancer microarray gene expression data sets (N = 1052). Survival analysis was pe...

Despite the relatively high frequency of somatic ERBB4 mutations in various cancer types, only a few activating ERBB4 mutations have been characterized, primarily due to lack of mutational hotspots in the ERBB4 gene. Here, we utilized our previously published pipeline, an in vitro screen for activating mutations, to perform an unbiased functional s...

Advances in sequencing technologies have facilitated the genetic characterization of large numbers of clinical cancer samples, leading to accumulation of extensive amounts of data. While potentially very useful for directing research and for clinical decision making, the increasing quantity of data generates challenges in its optimal management, an...

While targeted therapies can be effective for a subgroup of patients, identification of individuals who benefit from the treatments is challenging. At the same time, the predictive significance of the vast majority of the thousands of mutations observed in the cancer tissues remains unknown. Here, we describe the identification of novel predictive...

Receptor tyrosine kinase ERBB4 (HER4) is frequently mutated in human cancer, and ERBB4 mutations have been identified in patients relapsing on targeted therapy. Here, we addressed the functional consequences of recurrent cancer-associated ERBB4 mutations that are located at regions important for dimer interactions and/or are paralogous to known onc...

Despite clinical benefits of tyrosine kinase inhibitors (TKIs) in cancer, most tumors can reactivate proliferation under TKI therapy. Here we present transcriptional profiling of HER2+ breast cancer cells transitioning from dormant drug tolerant cells to re-proliferating cells under continuous HER2 inhibitor (HER2i) therapy. Focusing on phosphatase...

Genetic changes in the ERBB family of receptor tyrosine kinases serve as oncogenic driver events and predictive biomarkers for ERBB inhibitor drugs. ERBB3 is a pseudokinase member of the family that, although lacking a fully active kinase domain, is well known for its potent signaling activity as a heterodimeric complex with ERBB2. Previous studies...

The mechanisms promoting re-growth of dormant cancer cells under continuous tyrosine kinase inhibitor (TKI) therapy are poorly understood. Here we present transcriptional profiling of HER2+ breast cancer cells treated continuously with HER2 TKI (HER2i) therapy for 9 months. The data reveals specific gene regulatory programs associated with transiti...

Genetic changes in the ERBB family of receptor tyrosine kinases serve as oncogenic driver events and predictive biomarkers for ERBB inhibitor drugs. ERBB3 is a pseudokinase member of the family that, although lacking a fully active kinase domain, is well known for its potent signaling activity as a heterodimeric complex with ERBB2. Previous studies...

Activating mutations and copy number variations in ERBB genes have been shown to serve as oncogenic driver mutations and predictive biomarkers for ERBB inhibitor drugs. To address whether mutations in ERBB3 can affect the potential of ERBB3 to promote growth or affect sensitivity to ERBB inhibitors, we set up an unbiased functional screen for ERBB3...

Introduction: Cancer tissues harbor thousands of mutations, and a given oncogene may be mutated at hundreds of sites across different samples. The discovery of most of the currently known driver mutations has been facilitated by their accumulation in mutation hotspots within their respective genes. However, a vast majority of mutations in cancer ti...

Activating mutations and copy number variations in ERBB genes have been identified in several cancer types, and a number of cancer drugs targeting ERBB receptors have been approved for clinical use. These drugs include monoclonal antibodies (mAb) that selectively target either EGFR (ERBB1) or ERBB2 (HER2), and tyrosine kinase inhibitors (TKI) that...

p>Hundreds of somatic ERBB4 mutations have been described in cancer tissues with very limited information about their functional significance. However, analyses of individual mutants have indicated that activating ERBB4 mutations, such as ERBB4 K935I, do exist. Understanding the functional consequences of ERBB4 mutations is needed in order to asses...

Cancer tissues harbor thousands of mutations, and a given oncogene may be mutated at hundreds of sites across different samples. Most of these somatic mutations are expected to be inconsequential passenger mutations that reflect the general instability of the tumors. The discovery of most of the currently known driver mutations has been facilitated...

Cancer tissues harbor thousands of mutations, and a given oncogene may be mutated at hundreds of sites. Most of these somatic mutations are expected to be inconsequential passenger mutations that reflect the general instability of the tumors. The discovery of most of the currently known driver mutations has been facilitated by their accumulation in...

Abstract Therapeutic protocols including EGFR antibodies in the context of oxaliplatin-based regimens have variable clinical effect in colorectal cancer. Here, we tested the effect of the EGFR antibody cetuximab in different sequential combinations with oxaliplatin on the growth of colorectal cancer cells in vitro and in vivo. Cetuximab reduced the...

Background Receptor tyrosine kinases (RTK) are potential targets for the treatment of ischemic heart disease. The human RTK family consists of 55 members, most of which have not yet been characterized for expression or activity in the ischemic heart. Methods RTK gene expression was analyzed from human heart samples representing healthy tissue, acu...

Introduction: Cancer tissues harbor thousands of mutations while the current list of clinically validated actionable variants contains only about a dozen genetic markers. Most of the somatic mutations in cancer are expected to be inconsequential passenger mutations that reflect the general instability of the tumors. The discovery of most of the cur...

Table S2. TFs among iTreg DE Genes and TFBS on Their Promoters, Related to Figure 1

Table S3. HIC1 Knockdown DE Genes and the TFBS on Their Promoters, Related to Figure 3

The RNA-binding protein L1TD1 is one of the most specific and abundant proteins in pluripotent stem cells and is essential for the maintenance of pluripotency in human cells. Here, we identify the protein interaction network of L1TD1 in human embryonic stem cells (hESCs) and provide insights into the interactome network constructed in human pluripo...