Human epidermal growth factor receptor 2/neu as a novel therapeutic target in sinonasal undifferentiated carcinoma

Takahashi, Yoko; Lee, Junegoo; Pickering, Curtis R.; Bell, Diana; Jiffar, Tilahun; Myers, Jeffrey N.; Hanna, Ehab Y.; Kupferman, Michael E.

doi:10.1002/hed.24350

Cited by 16 publications

(20 citation statements)

References 31 publications

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“…We also identi ed copy gains in ERBB2 in 3/5 samples (Fig. 2b) suggesting a potential role of ERBB2 function in a subset of SNUCs, which has been previously noted (18). Moreover, we also identi ed copy number losses in SMARC family genes (SMARCA1, SMARCA2, SMARCA5, SMARCB1, SMARCC1 and SMARCE1) in numerous samples consistent with previous reports of the recurrence of alterations to this gene family in SNUC (16).…”

Section: Survival Analysissupporting

confidence: 89%

“…The patient derived SNUC cell line, MDA8788-6, was generously provided by MD Anderson. Generation of this cell line was previously described by Takahashi et.al (18). Cells were cultured in a humidi ed incubator at 37 °C with 5% (vol/vol) CO2 in DMEM with 10% FBS, 1X Pen/Strep, 1X NEAA.…”

Section: Cell Linementioning

confidence: 99%

“…The most commonly reported mutations include IDH2 and SMARCB1 which have been identi ed in small case series via traditional sequencing approaches or targeted sequencing panels (15)(16)(17). There have been additional case reports of potentially actionable mutations in isolated SNUCs including ERBB2 and FGFR1 (18,19), but previous efforts have been limited in their scope of sequencing (4) and currently there have been no comprehensive whole exome or genome sequencing studies performed on SNUCs.…”

Section: Introductionmentioning

confidence: 99%

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Genetic Analysis of Sinonasal Undifferentiated Carcinoma Discovers Recurrent SWI/SNF Alterations and a novel PGAP3-SRPK1 Fusion Gene

Neal

Birkeland

Bhangale

et al. 2020

Preprint

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Background: Sinonasal Undifferentiated Carcinoma (SNUC) is a rare and aggressive skull base tumor with poor survival and limited treatment options. To date, targeted sequencing studies have identified IDH2 and SMARCB1 as potential driver alterations, but the molecular alterations found in SMARCB1 wild type tumors are unknown.Methods: We evaluate survival outcomes in a cohort of 46 SNUC patients treated at an NCI designated cancer center and identify clinical and disease variables associated with survival on Kaplan-Meier and Cox multivariate survival analysis. We perform exome sequencing to characterize a series of SMARCB1 wild type tumors and cell line including identification of high confidence mutations, copy number alterations, microsatellite instability, and fusions. Knockdown studies using siRNA was utilized for validation of a novel PGAP3-SRPK1 gene fusion. Results: We discover recurrent aberrations to the SWI/SNF and FAT gene families. We also validate a novel PGAP3-SRPK1 gene fusion in the SNUC cell line, and show that knockdown of the fusion is negatively associated with EGFR, E2F and MYC signaling. Conclusion: Collectively, these data demonstrate recurrent alterations in the SWI/SNF and FAT gene families and discover a novel fusion gene (PGAP3-SRPK1). These data aim to improve understanding of possible driver mutations and guide future therapeutic strategies for this disease.

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Section: Survival Analysissupporting

confidence: 89%

Section: Cell Linementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Genetic Analysis of Sinonasal Undifferentiated Carcinoma Discovers Recurrent SWI/SNF Alterations and a novel PGAP3-SRPK1 Fusion Gene

Neal

Birkeland

Bhangale

et al. 2020

Preprint

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“…No HER2 overexpression was identified in the 11 SNUC cases examined, although it was reported in one study using an animal model. 55,56 SOX-2 amplification was shown in about one-third of SNUCs and other sinonasal cancers, such as SCC, and this may be associated with relapse after primary therapy. 57 There are also variable results regarding SNUC and HPV infection.…”

Section: Sinonasal Undifferentiated Carcinoma Example 7: Sinonasal Unmentioning

confidence: 99%

Updates on Immunohistochemical and Molecular Markers in Selected Head and Neck Diagnostic Problems

Yi¹,

Zhai²,

Wang³

2017

Archives of Pathology &Amp; Laboratory Medicine

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- Head and neck tumors include neoplasms originating from heterogeneous tissue. Using the selected clinical cases, this review illustrates a continuous development of emerging molecular-genetic techniques to assist in the interpretation of uncommon, often poorly differentiated, highly malignant neoplasms. The diagnostic results are appropriately transmitted to the oncologists, radiation oncologists, and surgeons to create a coordinated plan of care for patients with these unusual disorders affecting the head and neck.

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“…This could be due to prolonged incubation with lapatinib. Previous studies have shown decrease of growth factor expression in terms of relative protein expression following incubation with tyrosine kinase inhibitors [12,29].…”

Section: Discussionmentioning

confidence: 95%

Cytotoxic Effects of the Dual ErbB Tyrosine Kinase Inhibitor, Lapatinib, on Walker 256 Rat Breast Tumour and IEC-6 Rat Normal Small Intestinal Cell Lines

et al. 2019

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Lapatinib is an orally administered, dual ErbB1/ErbB2 tyrosine kinase inhibitor (TKI). It is effective in ErbB2 + ve breast cancer treatment. However, lapatinib is associated with diarrhoea with an incidence of 47-75%. The mechanism of ErbB1 TKI-induced diarrhoea remains unclear. ErbB1 or epidermal growth factor receptor (EGFR) is expressed in gastrointestinal mucosa whereby the primary site for drug absorption is intestine. Thus, administration of ErbB1 oral TKI may disrupt gut homeostasis, leading to diarrhoea. Nevertheless, further investigations are required. We observed that lapatinib inhibited 50% Walker 256 breast tumour cells and IEC-6 small intestinal cell growth. Higher percentage of necrosis was observed in lapatinib-treated Walker 256. Lapatinib-treated IEC-6 showed higher percentage of late apoptosis. Only ErbB2 mRNA was detected in Walker 256 but both ErbB1 and ErbB2 mRNAs were detected in IEC-6, yet both protein staining were detected in both cells. Lapatinib exhibited cytotoxic properties on ErbB1/ErbB2 expressing cell lines, with intestinal cells being more sensitive to lapatinib compared to tumour cells. Lapatinib induced necrosis in tumour cells, while inducing late apoptosis in intestinal cells may explain lapatinib-induced diarrhoea in patients administered with the drug which could be due to apoptosis of intestinal epithelial cells leading to barrier disruption and consequently diarrhoea.

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Human epidermal growth factor receptor 2/neu as a novel therapeutic target in sinonasal undifferentiated carcinoma

Abstract: Targeting HER2 may be a promising avenue for the development of novel therapies for SNUC. © 2016 Wiley Periodicals, Inc. Head Neck 38: E1926-E1934, 2016.

Cited by 16 publications

References 31 publications

Genetic Analysis of Sinonasal Undifferentiated Carcinoma Discovers Recurrent SWI/SNF Alterations and a novel PGAP3-SRPK1 Fusion Gene

Genetic Analysis of Sinonasal Undifferentiated Carcinoma Discovers Recurrent SWI/SNF Alterations and a novel PGAP3-SRPK1 Fusion Gene

Updates on Immunohistochemical and Molecular Markers in Selected Head and Neck Diagnostic Problems

Cytotoxic Effects of the Dual ErbB Tyrosine Kinase Inhibitor, Lapatinib, on Walker 256 Rat Breast Tumour and IEC-6 Rat Normal Small Intestinal Cell Lines

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