First name
Suzanne
Middle name
P
Last name
MacFarland

Title

Characteristics Associated with Tumor Development in Individuals Diagnosed with Beckwith-Wiedemann Spectrum: Novel Tumor-(epi)Genotype-Phenotype Associations in the BWSp Population.

Year of Publication

2021

Date Published

2021 11 21

ISSN Number

2073-4425

Abstract

<p>Beckwith-Wiedemann Spectrum (BWSp) is the most common epigenetic childhood cancer predisposition disorder. BWSp is caused by (epi)genetic changes affecting the BWS critical region on chromosome 11p15. Clinically, BWSp represents complex molecular and phenotypic heterogeneity resulting in a range of presentations from Classic BWS to milder features. The previously reported tumor risk based on Classic BWS cohorts is 8-10% and routine tumor screening has been recommended. This work investigated the tumor risk and correlation with phenotype within a cohort of patients from Classic BWS to BWSp using a mixed-methods approach to explore phenotype and epigenotype profiles associated with tumor development through statistical analyses with post-hoc retrospective case series review. We demonstrated that tumor risk across BWSp differs from Classic BWS and that certain phenotypic features are associated with specific epigenetic causes; nephromegaly and/or hyperinsulinism appear associated with cancer in some patients. We also demonstrated that prenatal and perinatal factors that are not currently part of the BWSp classification may factor into tumor risk. Additionally, blood testing results are not necessarily synonymous with tissue testing results. Together, it appears that the current understanding from Classic BWS of (epi)genetics and phenotype correlations with tumors is not represented in the BWSp. Further study is needed in this complex population.</p>

DOI

10.3390/genes12111839

Alternate Title

Genes (Basel)

PMID

34828445

Title

Genetic syndromes associated with endocrine tumors in children.

Year of Publication

2020

Number of Pages

150919

Date Published

2020 Jun

ISSN Number

1532-9453

Abstract

<p>Endocrine tumors comprise a variety of benign and malignant neoplasms that arise from the endocrine glands and neuroendocrine tissues. Functioning tumors are associated with typical clinical syndromes related to specific hormone(s) secreted, whereas nonfunctioning tumors present incidentally or secondary to symptoms related to mass effect. Endocrine tumors represent a minority of all neoplasms observed in the pediatric population and are generally associated with underlying hereditary syndromes. While most are clinically benign or low-grade cancers, a small percentage of endocrine tumors are high-grade malignancies requiring multimodal therapies. As with any rare childhood disease, treatment is best provided at tertiary care centers with multidisciplinary expertise in the management of such tumors.</p>

DOI

10.1016/j.sempedsurg.2020.150919

Alternate Title

Semin. Pediatr. Surg.

PMID

32571504

Title

Clinical utility of custom-designed NGS panel testing in pediatric tumors.

Year of Publication

2019

Number of Pages

32

Date Published

2019 May 28

ISSN Number

1756-994X

Abstract

<p><strong>BACKGROUND: </strong>Somatic genetic testing is rapidly becoming the standard of care in many adult and pediatric cancers. Previously, the standard approach was single-gene or focused multigene testing, but many centers have moved towards broad-based next-generation sequencing (NGS) panels. Here, we report the laboratory validation and clinical utility of a large cohort of clinical NGS somatic sequencing results in diagnosis, prognosis, and treatment of a wide range of pediatric cancers.</p>

<p><strong>METHODS: </strong>Subjects were accrued retrospectively at a single pediatric quaternary-care hospital. Sequence analyses were performed on 367 pediatric cancer samples using custom-designed NGS panels over a 15-month period. Cases were profiled for mutations, copy number variations, and fusions identified through sequencing, and their clinical impact on diagnosis, prognosis, and therapy was assessed.</p>

<p><strong>RESULTS: </strong>NGS panel testing was incorporated meaningfully into clinical care in 88.7% of leukemia/lymphomas, 90.6% of central nervous system (CNS) tumors, and 62.6% of non-CNS solid tumors included in this cohort. A change in diagnosis as a result of testing occurred in 3.3% of cases. Additionally, 19.4% of all patients had variants requiring further evaluation for potential germline alteration.</p>

<p><strong>CONCLUSIONS: </strong>Use of somatic NGS panel testing resulted in a significant impact on clinical care, including diagnosis, prognosis, and treatment planning in 78.7% of pediatric patients tested in our institution. Somatic NGS tumor testing should be implemented as part of the routine diagnostic workup of newly diagnosed and relapsed pediatric cancer patients.</p>

DOI

10.1186/s13073-019-0644-8

Alternate Title

Genome Med

PMID

31133068

Title

Disease Burden and Outcome in Pediatric and Young Adults with Concurrent Graves Disease and Differentiated Thyroid Carcinoma.

Year of Publication

2018

Date Published

2018 May 18

ISSN Number

1945-7197

Abstract

<p><strong>Context: </strong>Adults with differentiated thyroid carcinoma (DTC) and Graves Disease (GD) demonstrate a greater reported disease burden and aggressive DTC behavior. To date, no studies have examined the impact and long-term outcome of concurrent GD and DTC (GD-DTC) in pediatric and young adults.</p>

<p><strong>Design: </strong>Single institution, retrospective longitudinal cohort study between 1997-2016.</p>

<p><strong>Participants: </strong>139 pediatric and young adults with DTC, diagnosed at median age 15 (range 5-23) years compared to 12 GD-DTC patients, median age 18 (range 12-20) years.</p>

<p><strong>Major Outcome Measures: </strong>Patient demographics, pre-operative imaging, fine needle aspiration (FNA) cytology, operative and pathological reports, laboratory studies, treatment, and subsequent 2-year outcomes.</p>

<p><strong>Results: </strong>Compared to DTC, GD-DTC were significantly older at the time of DTC diagnosis (p&lt;0.01). GD-DTC were more likely to exhibit micro-carcinoma (p&lt;0.01) and 2/12 (17%) demonstrated tall-cell variant PTC vs 2/139 (2%) in DTC alone (p=0.03). While DTC patients showed greater lymphovascular invasion (60% vs 25%; p=0.03), no group differences were noted in extra-thyroidal extension, regional lymph node, distant or lung metastasis. There were no group differences in the 2-year outcome for remission, persistent disease, or recurrence.</p>

<p><strong>Conclusions: </strong>Concurrent DTC in pediatric GD patients is not associated with a greater disease burden at presentation and shows no significant difference in 2-year outcomes compared to DTC alone. Similar to adults, micro-carcinoma and tall-cell variant PTC is prevalent in pediatric GD-DTC. For GD-DTC patients with an identified nodule on ultrasound imaging prior to definitive therapy, FNA biopsy is recommended to guide definitive treatment.</p>

DOI

10.1210/jc.2018-00026

Alternate Title

J. Clin. Endocrinol. Metab.

PMID

29788090

Title

Management of adrenal masses in patients with Beckwith-Wiedemann syndrome.

Year of Publication

2017

Date Published

2017 Jan 09

ISSN Number

1545-5017

Abstract

<p>Beckwith-Wiedemann syndrome (BWS) is a genetic overgrowth and cancer predisposition syndrome, associated with both benign and malignant adrenal findings. Literature review and an institutional case series elucidate the wide spectrum of adrenal findings in BWS patients. The altered expression of the 11p15 region is likely related to adrenal gland hyperplasia and growth dysregulation. Given the absence of guidelines for managing adrenal findings in BWS, we propose a systematic approach to adrenal findings in BWS patients, to allow for maximum detection of potentially malignant pathology without posing additional risk to patients.</p>

DOI

10.1002/pbc.26432

Alternate Title

Pediatr Blood Cancer

PMID

28066990

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