Advanced Search
Current and Breaking News for Professionals, Consumers and Media




Cancer Issues Author: Staff Editor Last Updated: Apr 23, 2018 - 10:22:06 AM



CHIPing Away at Cancer Tumors Through Genomic Analysis

By Staff Editor
Apr 23, 2018 - 10:14:06 AM



Email Newsletter icon, E-mail Newsletter icon, Email List icon, E-mail List icon Sign up for our Ezine
For Email Marketing you can trust


Email this article
 Printer friendly page

(HealthNewsDigest.com) - New Brunswick, N.J. – April 23, 2018 –
Investigators in the Rutgers Cancer Institute of New Jersey Precision Medicine Program, in collaboration with researchers at Foundation Medicine, Inc. (Morrisville, North Carolina and Cambridge, Massachusetts), have discovered that some mutations detected in comprehensive, clinical genome sequencing of patients with solid tumors do not originate from cancer cells, but arise from mutated hematopoietic cells that infiltrate the tumor microenvironment. The findings, say investigators, have direct implications for cancer patients, specifically in accurately interpreting their molecular testing results and ensuring that treatment is focused on somatic tumor-specific mutations.

Rutgers Cancer Institute researcher Hossein Khiabanian, PhD, an assistant professor of pathology and laboratory medicine at Rutgers Robert Wood Johnson Medical School, and Shridar Ganesan, MD, PhD, associate director for translational science and chief of molecular oncology at Rutgers Cancer Institute, associate professor of medicine and pharmacology at Rutgers Robert Wood Johnson Medical School, and the Omar Boraie Chair in Genomic Science, are the co-corresponding authors on the work. Rutgers Cancer Institute researcher Gregory Riedlinger, MD, PhD, an assistant professor of pathology and laboratory medicine at Rutgers Robert Wood Johnson Medical School is a lead author on this work. They share more about the research published in the April 20 online edition of Blood (doi: 10.1182/blood-2018-03-840629):

Q:  Why is this topic important to explore?

A: With the advent of precision oncology and implementation of clinically certified sequencing assays, physicians have gained access to the genetic profiles of individual cancers. However, when tumor specimens are sequenced, the DNA from both cancer and non-tumor cells, including mixed blood cells is analyzed. We noticed that in some solid tumor specimens there were mutations in genes commonly found mutated in myeloid disorders; these mutations were often present at low levels compared to the amount of tumor. We hypothesized that these mutations were due to an age-related condition known as clonal hematopoiesis of indeterminate potential (or CHIP) in which mutations are found in blood cells, but a hematologic cancer is not diagnosed. CHIP was first identified in peripheral blood of healthy individuals and its prevalence is shown to increase with age, especially after age 70 when it is detectable in about 10 percent of the population. CHIP is associated with an elevated risk of overall mortality, particularly from cardiovascular causes, and has been shown to increase the risk of developing therapy-related myeloid neoplasms. The identification of CHIP is important for correct interpretation of clinical tumor sequencing results and for predicting related hematologic adverse events.

Q:  How did you approach this work and what did you discover?

A: We collaborated with scientists at Foundation Medicine and analyzed 113,079 solid tumors, the largest known cohort to date, to identify the genes with the highest rate of detected mutations in older patients. Our statistical analysis showed that of 257 genes, only mutations in the DNMT3ATET2SF3B1, and ASXL1 genes were detected at higher rates in older patients’ solid tumors, independent of their cancer type. These four genes are known to be associated with CHIP. To confirm that these mutations originated from hematopoietic cells mixed in the tumor microenvironment, we examined 1,636 specimens analyzed at Rutgers Cancer Institute. Of note was a patient diagnosed with two independent lung cancers of different histology and distinct sets of genomic alterations. The only commonality between the specimens was two identical mutations in the DNMT3A and TET2 genes, which were detected at low levels. When we analyzed hematopoietic cells from this patient, we detected the same mutations and confirmed that they were present in blood cells rather than in lung cancer cells. In 79 percent of the cases (11 out of 14), sequencing patient-matched peripheral blood samples demonstrated a hematopoietic origin of the mutation in the DNMT3A and TET2 genes.

Q:  What are the implications of these findings?

A: Our results demonstrate that not all detected mutations in clinical sequencing assays originate from tumor cells. Our analyses of solid tumors from a broad array of cancer subtypes strongly suggest that many genomic alterations in DNMT3ATET2ASXL1, and SF3B1 detected in solid tumor samples arise from their presence in admixed hematopoietic elements, especially when detected at low abundances. Recognizing CHIP is critical for interpreting clinical sequencing data from individual patients to ensure that precision medicine strategies are not incorrectly focused on non-tumor genomic alterations, and to identify patients at risk for developing therapy-related myeloid neoplasms. As the clinical utilization of tumor-only sequencing assays increases, it is imperative to realize that CHIP may be detected in solid tumor microenvironment and highlight CHIP-associated mutations in clinical sequencing reports. Our team is now focused on characterizing CHIP under solid tumor treatment with the potential to move molecular prediction of therapy-related adverse events to the forefront of clinical practice.

The research was supported by the Comprehensive Genomics, Biomedical Informatics, and Biospecimen Repository Shared Resources at Rutgers Cancer Institute of New Jersey (P30CA072720) as well as Rutgers Office of Advanced Research Computing (NIH 1S10OD012346-01A1).  Other support/acknowledgements can be found at http://www.bloodjournal.org/content/early/2018/04/19/blood-2018-03-840629?sso-checked=true.

###



Top of Page

HealthNewsDigest.com

Cancer Issues
Latest Headlines


+ Cancer and Mental Health
+ Immunotherapy Drug Shows Continued Promise in Several Advanced-Stage Cancers
+ Find New Mechanism to Turn on Cancer-Killing T Cells
+ Back to the Trails After Cancer Rehabilitation
+ Breakthrough COVID Infections More Likely in Cancer and Alzheimer’s Patients
+ Consider all Treatment Options for Ovarian Cancer
+ Men Need to Take Melanoma Seriously
+ Melanoma a Higher Risk for Older Veterans
+ Precision Medicine Approach to Metabolic Therapy for Breast Cancer
+ Test for Multiple Myeloma Provides Clues of a Rare, More Deadly Type



Contact Us | Job Listings | Help | Site Map | About Us
Advertising Information | HND Press Release | Submit Information | Disclaimer

Site hosted by Sanchez Productions