<scp>HER2</scp> evaluation for clinical decision making in human solid tumours: pearls and pitfalls

Zhang, Huina; Finkelman, Brian S; Ettel, Mark G; Velez, Moises J; Turner, Bradley M; Hicks, David G

doi:10.1111/his.15170

Cited by 2 publications

(1 citation statement)

References 117 publications

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“…This revealed that the most frequently named gene in titles and abstracts by far is ERBB2 in Chr17q21 (35,121 PubMed hits), which accounts for 2/3 of the total, where the next most frequently named gene in the same Chr17q21 region is CDK12 (413 PubMed hits) ( Supplementary Table 1 ). ERBB2 encodes Human Epidermal Growth Factor Receptor 2 (HER2), which is commonly amplified in breast and other tumors and is a target of therapy (26). As our measures of hypertranscription are scaled to the human genome sequence, amplification of a region will appear as a proportional increase in the level of RNAPII over the amplified region, so that we can interpret regional hypertranscription in both our Br and Co tumor samples as revealing independent amplification events.…”

Section: Resultsmentioning

confidence: 99%

RNA Polymerase II hypertranscription in cancer FFPE samples

Henikoff,

Paranal

et al. 2024

Preprint

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Hypertranscription occurs at targets of oncogene transcription factors in aggressive human cancers. However detection relies on mRNAs, which are heavily processed and have variable half-lives, and on accurate cell number estimations. Previously we introduced FFPE-CUTAC, a genome-wide method for mapping RNA Polymerase II in formalin-fixed paraffin-embedded (FFPE) sections. Here we apply FFPE-CUTAC on slides and curls to quantify hypertranscription at regulatory elements and replication-coupled histone genes. We find that hypertranscription differs between different transgene-driven mouse gliomas and scales with enhanced proliferation and reduced mitochondrial DNA. We also apply FFPE-CUTAC to identify tumor-specific patterns in assorted human tumor-normal pairs. We analyze the top-ranked 100 annotated regulatory elements that are hypertranscribed in most of the tumors and identify multiple loci around ERBB2 on Chromosome 17q12-21 in the breast and colon cancer samples, mapping likely HER2 amplifications. Our results demonstrate that FFPE-CUTAC measurement of hypertranscription provides an affordable genome-wide strategy for cancer diagnosis.

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Section: Resultsmentioning

confidence: 99%

RNA Polymerase II hypertranscription in cancer FFPE samples

Henikoff,

Paranal

et al. 2024

Preprint

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Prognostic and Predictive Roles of HER2 Status in Non-Breast and Non-Gastroesophageal Carcinomas

Quaquarini,

Grillo,

Gervaso

et al. 2024

Cancers

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The oncogene ERBB2, also known as HER2 or c-ERB2, is located on chromosome 17 (q12). It encodes a tyrosine kinase receptor, the human epidermal growth factor receptor 2 (HER2), involved in neoplastic proliferation, tumor angiogenesis, and invasiveness. Over the past years, the introduction of various anti-HER2 therapies has significantly improved outcomes for patients with HER2-positive breast and gastroesophageal carcinomas. More recently, the introduction of a new antibody–drug conjugate, that is trastuzumab deruxtecan, expanded the therapeutic options to low-HER2 breast and gastroesophageal tumors. HER2 protein overexpression is investigated using immunohistochemistry, gene amplification using fluorescence in situ hybridization, and gene mutation using next-generation sequencing. This review evaluated the predictive and prognostic role of HER2 status in various types of epithelial malignant cancers beyond breast and gastroesophageal cancers. We critically analyzed the key published studies, focusing on utilized scoring systems and assays used, and analyzed clinical parameters and therapeutic approaches. Although the evidence about prognostic and predictive roles of HER2 in carcinomas other than breast and gastroesophageal has been widely increasing over the last decade, it still remains investigational, revealing a tumor site-related prognostic and predictive value of the different types of HER2 alterations. However, standardized and validated scoring system assays have not been well-established for many organs.

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HER2 evaluation for clinical decision making in human solid tumours: pearls and pitfalls

Cited by 2 publications

References 117 publications

RNA Polymerase II hypertranscription in cancer FFPE samples

RNA Polymerase II hypertranscription in cancer FFPE samples

Prognostic and Predictive Roles of HER2 Status in Non-Breast and Non-Gastroesophageal Carcinomas

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