Beare-Stevenson cutis gyrata syndrome: A new case of a c.1124C↷G (Y375C) mutation in the FGFR2 gene

Fonseca, Renata; Costa-Lima, Marcelo Aguiar; Pereira, Eliana Ternes; Castilla, Eduardo E.; Orioli, Iêda M.

doi:10.3892/mmr_00000024

Cited by 7 publications

(5 citation statements)

References 22 publications

(31 reference statements)

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“…A summation of all audiological series of Beare Stevenson syndrome reveals hearing loss in 1/26 patients (4%). Of these 26 patients reported to date, 24 have descriptions of the physical examination of the ear [40,61,62,[64][65][66][67][68][69][70][71][72][73][74][75][76][77][78]. Of these 24 patients, only one patient was not described as having ear malformations.…”

Section: Jackson-weiss Syndrome Beare-stevenson Syndrome and Crouzonmentioning

confidence: 99%

Hearing loss in syndromic craniosynostoses: Otologic manifestations and clinical findings

Agochukwu

Solomon

Muenke

2014

International Journal of Pediatric Otorhinolaryngology

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Section: Jackson-weiss Syndrome Beare-stevenson Syndrome and Crouzonmentioning

confidence: 99%

Hearing loss in syndromic craniosynostoses: Otologic manifestations and clinical findings

Agochukwu

Solomon

Muenke

2014

International Journal of Pediatric Otorhinolaryngology

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“…For example, subject 1 was found to have two somatic activating mutations affecting FGFR2 , with predicted amino acid substitutions at S252W 33 and Y375C. 34 Off-label treatment with ponatinib produced a significant but short-lived reduction in cutaneous tumor infiltrates, lasting only 7 weeks. These early findings lead to the adoption of multiagent regimens.…”

Section: Resultsmentioning

confidence: 99%

Safety, Feasibility, and Merits of Longitudinal Molecular Testing of Multiple Metastatic Sites to Inform mTNBC Patient Treatment in the Intensive Trial of Omics in Cancer

Burton

Mahen

Konnick

et al. 2022

JCO Precision Oncology

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PURPOSE Patients with metastatic triple-negative breast cancer (mTNBC) have poor outcomes. The Intensive Trial of Omics in Cancer (ITOMIC) sought to determine the feasibility and potential efficacy of informing treatment decisions through multiple biopsies of mTNBC deposits longitudinally over time, accompanied by analysis using a distributed network of experts. METHODS Thirty-one subjects were enrolled and 432 postenrollment biopsies performed (clinical and study-directed) of which 332 were study-directed. Molecular profiling included whole-genome sequencing or whole-exome sequencing, cancer-associated gene panel sequencing, RNA-sequencing, and immunohistochemistry. To afford time for analysis, subjects were initially treated with cisplatin (19 subjects), or another treatment they had not received previously. The results were discussed at a multi-institutional ITOMIC Tumor Board, and a report transmitted to the subject's oncologist who arrived at the final treatment decision in conjunction with the subject. Assistance was provided to access treatments that were predicted to be effective. RESULTS Multiple biopsies in single settings and over time were safe, and comprehensive analysis was feasible. Two subjects were found to have lung cancer, one had carcinoma of unknown primary site, tumor samples from three subjects were estrogen receptor–positive and from two others, human epidermal growth factor receptor 2–positive. Two subjects withdrew. Thirty-four of 112 recommended treatments were accessed using approved drugs, clinical trials, and single-patient investigational new drugs. After excluding the three subjects with nonbreast cancers and the two subjects who withdrew, 22 of 26 subjects (84.6%) received at least one ITOMIC Tumor Board–recommended treatment. CONCLUSION Further exploration of this approach in patients with mTNBC is merited.

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“…Here, we demonstrated that FGFR2 Y375C, in the juxtamembrane domain of FGFR2 (exon 11), is an activating mutation that enhances the growth of MCF10A normal-like breast cells. Y375C mutations were previously described as heterozygous germline mutations in newborns with caudal appendages and craniosynostosis and have been postulated to activate these conditions [51][52][53][54][55] . Although Y375C mutations are uncommon, they have been reported in multiple tumor types 1,26,56,57 .…”

Section: Discussionmentioning

confidence: 99%

Efficacy of futibatinib, an irreversible fibroblast growth factor receptor inhibitor, in FGFR-altered breast cancer

Saridogan,

Akcakanat,

Zhao

et al. 2023

Sci Rep

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Several alterations in fibroblast growth factor receptor (FGFR) genes have been found in breast cancer; however, they have not been well characterized as therapeutic targets. Futibatinib (TAS-120; Taiho) is a novel, selective, pan-FGFR inhibitor that inhibits FGFR1-4 at nanomolar concentrations. We sought to determine futibatinib’s efficacy in breast cancer models. Nine breast cancer patient–derived xenografts (PDXs) with various FGFR1-4 alterations and expression levels were treated with futibatinib. Antitumor efficacy was evaluated by change in tumor volume and time to tumor doubling. Alterations indicating sensitization to futibatinib in vivo were further characterized in vitro. FGFR gene expression between patient tumors and matching PDXs was significantly correlated; however, overall PDXs had higher FGFR3-4 expression. Futibatinib inhibited tumor growth in 3 of 9 PDXs, with tumor stabilization in an FGFR2-amplified model and prolonged regression (> 110 days) in an FGFR2 Y375C mutant/amplified model. FGFR2 overexpression and, to a greater extent, FGFR2 Y375C expression in MCF10A cells enhanced cell growth and sensitivity to futibatinib. Per institutional and public databases, FGFR2 mutations and amplifications had a population frequency of 1.1%–2.6% and 1.5%–2.5%, respectively, in breast cancer patients. FGFR2 alterations in breast cancer may represent infrequent but highly promising targets for futibatinib.

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Beare-Stevenson cutis gyrata syndrome: A new case of a c.1124C↷G (Y375C) mutation in the FGFR2 gene

Cited by 7 publications

References 22 publications

Hearing loss in syndromic craniosynostoses: Otologic manifestations and clinical findings

Hearing loss in syndromic craniosynostoses: Otologic manifestations and clinical findings

Safety, Feasibility, and Merits of Longitudinal Molecular Testing of Multiple Metastatic Sites to Inform mTNBC Patient Treatment in the Intensive Trial of Omics in Cancer

Efficacy of futibatinib, an irreversible fibroblast growth factor receptor inhibitor, in FGFR-altered breast cancer

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