We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
Technopath Clinical Diagnostics

Illumina

Illumina develops, manufactures and markets integrated systems for the analysis of genetic variations and biological ... read more Featured Products: More products

Download Mobile App




Events

ATTENTION: Due to the COVID-19 PANDEMIC, many events are being rescheduled for a later date, converted into virtual venues, or altogether cancelled. Please check with the event organizer or website prior to planning for any forthcoming event.
05 Mar 2022 - 09 Mar 2022
Virtual Venue

Intratumor Heterogeneity Analyzed in Neuroblastoma

By LabMedica International staff writers
Posted on 22 Dec 2021
Print article
Image: Histopathology of a typical neuroblastoma with rosette formation (Photo courtesy of Dr. Mark Applebaum, MD)
Image: Histopathology of a typical neuroblastoma with rosette formation (Photo courtesy of Dr. Mark Applebaum, MD)
Neuroblastoma is the most common solid pediatric tumour, accounting for 15% of cancer-related deaths in early childhood and especially for patients directly diagnosed with high-risk neuroblastoma have a poor prognosis.

Tumors are heterogeneous, which means that different parts of the same tumor can be genetically distinct. This phenomenon, known as intratumor heterogeneity, is steadily gaining in significance within the field of oncology. Cellular and molecular differences within the same tumor play an important role in many different cancers due to their implications for diagnosis and the use of targeted therapies.

A large team of pediatric oncologists at the Charité-Universitätsmedizin Berlin (Berlin, Germany) and their colleagues collected tumor samples from 10 patients who were enrolled in a study between 2014 and 2018. Samples were collected by open surgical biopsy either at diagnosis, at tumour resection after 4–6 cycles of chemotherapy or at diagnosis of relapse. Fresh samples were immediately snap-frozen in liquid nitrogen and stored at −80 °C. Portions of tumour material were formalin-fixed and paraffin-embedded (FFPE) in parallel for diagnostics and preservation in the pathology unit. The team analyzed a total of 140 neuroblastoma samples.

Peripheral blood collected from each patient was used as a matched germline control for tumor samples. DNA was prepared using the Qiagen DNA Mini kit (Qiagen, Venlo, the Netherlands). The SureSelect Human All Exon V6 kit (Agilent Technologies, Santa Clara, CA, USA) was used to prepare libraries enriched with exonic sequences. The libraries were further prepared for sequencing using the Illumina TruSeq Exome Kit and sequenced on Illumina HiSeq 2500 and Illumina NextSeq sequencers (Illumina, San Diego, CA, USA). A list of genes potentially involved in neuroblastoma development was compiled by combining lists of potential cancer driver genes from several sources.

The investigators focused their analysis on the neuroblastoma-associated genes ALK, MYCN and FGFR1, which play an important role in both clinical course and treatment. According to their results, changes in the ALK and MYCN genes were not present continuously throughout the course of the disease, nor were they found in all tumor cells. Changes in the ALK and FGFR1 genes can offer useful treatment targets, particularly in relapsed patients. They found that, in some patients, ALK mutations which were present at the time of diagnosis had disappeared by the time the tumor was surgically removed. Changes in the FGFR1 gene were only found in distinct tumor regions. The scientists were also able to identify an instability in the number of gene copies present in neuroblastoma cells.

Angelika Eggert, MD, a Professor of Pediatric Oncology and a senior author of the study, said, “We are now in a better position to understand how neuroblastoma cells behave. This knowledge is essential in relation to patients who suffer a recurrence of their disease because their treatment often requires the use of personalized and targeted therapies. When a tumor presents as genetically heterogeneous, targeted molecular therapy may well capture a majority of the abnormal tissue but, crucially, will not capture all of the affected cells. The cancer will then be able to regrow from those remaining cells.”

The authors conclude that their in-depth analysis of neuroblastoma intratumor heterogeneity reveals that extensive genetic heterogeneity and subclonal diversification evolves under therapy and may have important implications for the clinical interpretation of molecular diagnostic results and for the selection of appropriate second-line treatment approaches. The study was published on November 23, 2021 in the journal Nature Communications.

Related Links:
Charité-Universitätsmedizin Berlin
Qiagen
Agilent Technologies
Illumina


Gold Supplier
TBI Blood Test
i-STAT TBI Plasma Test
New
Urine Analyzer
ComboStik R-50
New
Coagulation Analyzer
DIAcheck C1
New
Automated Nucleic Acid Extraction System
MAGNETITE

Print article
IIR Middle East

Channels

Hematology

view channel
Image: My Qualiris QC (Photo courtesy of Stago)

Stago Launches New My Qualiris QC Website for Brand-New User Experience

Stago (Paris, France) has launched its new My Qualiris QC website which provides a brand-new user experience with a 24/7 accessible web-application where the results of a user’s network are only a few clicks away.... Read more

Industry

view channel
Illustration

Global Immunofluorescence Assay (IFA) Market to Surpass USD 4 Billion by 2028 Due to Growing Burden of Infectious Diseases

The global immunofluorescence assay (IFA) market is expected to reach USD 4.01 billion by 2028, driven by the increasing global healthcare burden of chronic and infectious diseases, rising application... Read more
Copyright © 2000-2022 Globetech Media. All rights reserved.