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Amplification of ERBB2 (HER2) in embryonal rhabdomyosarcoma : A potential treatment target in rare cases?

Mitra, Shamik LU ; Sydow, Saskia LU ; Magnusson, Linda LU ; Piccinelli, Paul LU ; Törnudd, Lisa ; Øra, Ingrid LU ; Ljungman, Gustaf ; Sandgren, Johanna ; Gisselsson, David LU and Mertens, Fredrik LU (2022) In Genes, Chromosomes and Cancer 61(1). p.5-9
Abstract

The ERBB2 gene encodes a receptor tyrosine kinase also known as HER2. The gene is amplified and overexpressed in one-fifth of breast carcinomas; patients with such tumors benefit from targeted treatment with trastuzumab or other drugs blocking the receptor. In addition, ERBB2 has been shown to be amplified and/or overexpressed in a variety of other malignancies. Notably, both alveolar and embryonal rhabdomyosarcoma (RMS), especially in children, often show increased expression of ERBB2. Although high-level amplification of the gene has not been described in RMS, its frequent expression at the cell surface of RMS cells has been exploited for chimeric antigen receptor T-cell (CAR T)-based treatment strategies. We here describe two cases... (More)

The ERBB2 gene encodes a receptor tyrosine kinase also known as HER2. The gene is amplified and overexpressed in one-fifth of breast carcinomas; patients with such tumors benefit from targeted treatment with trastuzumab or other drugs blocking the receptor. In addition, ERBB2 has been shown to be amplified and/or overexpressed in a variety of other malignancies. Notably, both alveolar and embryonal rhabdomyosarcoma (RMS), especially in children, often show increased expression of ERBB2. Although high-level amplification of the gene has not been described in RMS, its frequent expression at the cell surface of RMS cells has been exploited for chimeric antigen receptor T-cell (CAR T)-based treatment strategies. We here describe two cases of pediatric, fusion-negative embryonal RMS with high-level amplification of the ERBB2 gene. One patient is currently treated with conventional chemotherapy for a recently detected standard risk RMS, whereas the other patient died from metastatic disease. Both tumors displayed focal amplicons (210 and 274 Kb, respectively) in chromosome band 17q12, with proximal and distal borders corresponding to those typically seen in breast cancer. In both tumors, the ERBB2 amplicon correlated with high expression at the RNA and protein levels. Thus, breast cancer-like ERBB2 amplification is a very rare, but recurrent feature of pediatric RMS, and should be exploited as an alternative treatment target.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Genes, Chromosomes and Cancer
volume
61
issue
1
pages
5 - 9
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:34418214
  • scopus:85114029995
ISSN
1045-2257
DOI
10.1002/gcc.22996
language
English
LU publication?
yes
id
eb7cd788-4298-47e9-bc0b-d58721102977
date added to LUP
2021-09-06 08:25:38
date last changed
2024-06-01 14:59:18
@article{eb7cd788-4298-47e9-bc0b-d58721102977,
  abstract     = {{<p>The ERBB2 gene encodes a receptor tyrosine kinase also known as HER2. The gene is amplified and overexpressed in one-fifth of breast carcinomas; patients with such tumors benefit from targeted treatment with trastuzumab or other drugs blocking the receptor. In addition, ERBB2 has been shown to be amplified and/or overexpressed in a variety of other malignancies. Notably, both alveolar and embryonal rhabdomyosarcoma (RMS), especially in children, often show increased expression of ERBB2. Although high-level amplification of the gene has not been described in RMS, its frequent expression at the cell surface of RMS cells has been exploited for chimeric antigen receptor T-cell (CAR T)-based treatment strategies. We here describe two cases of pediatric, fusion-negative embryonal RMS with high-level amplification of the ERBB2 gene. One patient is currently treated with conventional chemotherapy for a recently detected standard risk RMS, whereas the other patient died from metastatic disease. Both tumors displayed focal amplicons (210 and 274 Kb, respectively) in chromosome band 17q12, with proximal and distal borders corresponding to those typically seen in breast cancer. In both tumors, the ERBB2 amplicon correlated with high expression at the RNA and protein levels. Thus, breast cancer-like ERBB2 amplification is a very rare, but recurrent feature of pediatric RMS, and should be exploited as an alternative treatment target.</p>}},
  author       = {{Mitra, Shamik and Sydow, Saskia and Magnusson, Linda and Piccinelli, Paul and Törnudd, Lisa and Øra, Ingrid and Ljungman, Gustaf and Sandgren, Johanna and Gisselsson, David and Mertens, Fredrik}},
  issn         = {{1045-2257}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{5--9}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Genes, Chromosomes and Cancer}},
  title        = {{Amplification of ERBB2 (HER2) in embryonal rhabdomyosarcoma : A potential treatment target in rare cases?}},
  url          = {{http://dx.doi.org/10.1002/gcc.22996}},
  doi          = {{10.1002/gcc.22996}},
  volume       = {{61}},
  year         = {{2022}},
}