DICER1 and FOXL2 Mutation Status Correlates With Clinicopathologic Features in Ovarian Sertoli-Leydig Cell Tumors.

08:00 EDT 1st May 2019 | BioPortfolio

Summary of "DICER1 and FOXL2 Mutation Status Correlates With Clinicopathologic Features in Ovarian Sertoli-Leydig Cell Tumors."

Sertoli-Leydig cell tumors (SLCTs) are rare ovarian sex cord-stromal neoplasms. The only known recurrent genetic abnormality is DICER1 mutation, with rare mutations reported in FOXL2. We set out to establish a molecular classifier using DICER1 and FOXL2 somatic mutation status and clinicopathologic features in 42 SLCTs. Five tumors (12%) were well differentiated, 31 (74%) moderately differentiated, and 6 (14%) poorly differentiated. Eight (19%) had heterologous elements, and 2 (5%) showed retiform differentiation; all 10 were moderately differentiated. DICER1 RNase IIIb domain mutations were identified in 18/41 (44%; 17 moderately, 1 poorly differentiated), including all cases with retiform or heterologous elements. FOXL2 c.402C>G (p.C134W) mutation was identified in 8/42 (19%) tumors (5 moderately, 3 poorly differentiated). DICER1 and FOXL2 mutations were mutually exclusive. Median age for the cohort was 47 years (range, 15 to 90 y). Patients with DICER1 mutations were younger (median, 24.5 y; range, 15 to 62 y) than patients with FOXL2 mutation (median, 79.5 y; range, 51 to 90 y) (P<0.0001). Nine of 10 tumors with retiform or heterologous elements occurred in premenopausal patients (median, 26.5 y; range, 15 to 57 y). Patients with tumors that were wild type for DICER1 and FOXL2 (15/42, 37%) had an intermediate age (median, 51 y; range, 17 to 74 y). All tumors were FOXL2 positive by immunohistochemistry. Patients with FOXL2 mutation trended toward presenting more often with abnormal bleeding (P=0.13); DICER1-mutant patients trended toward having more androgenic symptoms (P=0.22). Our data suggest at least 3 molecular subtypes of SLCT with distinct clinicopathologic features: DICER1 mutant (younger, more androgenic symptoms, moderately/poorly differentiated, retiform or heterologous elements), FOXL2 mutant (postmenopausal, abnormal bleeding, moderately/poorly differentiated, no retiform or heterologous elements), and DICER1/FOXL2 wild type (intermediate age, no retiform or heterologous elements, including all well-differentiated tumors).


Journal Details

This article was published in the following journal.

Name: The American journal of surgical pathology
ISSN: 1532-0979
Pages: 628-638


DeepDyve research library

PubMed Articles [12315 Associated PubMed Articles listed on BioPortfolio]

Sex cord-stromal tumors of the ovary : Current aspects with a focus on granulosa cell tumors, Sertoli-Leydig cell tumors, and gynandroblastomas.

Sex cord-stromal tumors of the ovary (SCSTO) comprise a heterogeneous and fascinating group of neoplasms with diverse clinicopathological features, including benign lesions as well as tumors with mal...

Identification of Homozygous Somatic DICER1 Mutation in Pleuropulmonary Blastoma.

Pleuropulmonary blastoma (PPB) is a rare, progressive, and aggressive malignant intrathoracic tumor observed during childhood. Mutations in the DICER1 gene have been considered a major etiologic facto...

An update on the central nervous system manifestations of DICER1 syndrome.

DICER1 syndrome is a rare tumor predisposition syndrome with manifestations that predominantly affect children and young adults. The syndrome is typically caused by heterozygous germline loss-of-funct...

High Preponderance of BRAF V600E Mutation in Papillary Thyroid Carcinoma Among Filipinos: A Clinicopathologic Study.

BRAF mutation in papillary thyroid carcinoma (PTC) is associated with an aggressive phenotype, with varying incidence. We evaluated the prevalence of BRAF mutations in PTC among Filipino patients and ...

Long-term outcomes of follicular variant vs classic papillary thyroid carcinoma.

The majority of papillary thyroid carcinoma (PTC) cases comprise classic papillary (C-PTC) and follicular variant (FV-PTC) histologic sub-types. Historically, clinical equivalency was assumed, but rec...

Clinical Trials [4683 Associated Clinical Trials listed on BioPortfolio]

International PPB Registry for PPB, DICER1 and Associated Conditions

Pleuropulmonary blastoma (PPB) is a rare malignant neoplasm of the lung presenting in early childhood. Type I PPB is a purely cystic lesion, Type II is a partially cystic, partially solid ...

Overall and Disease Specific Survival in Patients With Confirmed MEN1 With or Without PNET (Pancreatic Neuroendocrine Tumors)

OBJECTIVES: The primary objective of this study is to evaluate the effect of estrogen on the development of the PNET in MEN1 patients. The secondary objective is to evaluate the ov...

A Retrospective Molecular Epidemiology Study in Singapore Patients With Advanced Non Small Cell Lung Cancer (NSCLC) of Adenocarcinoma Histology to Assess Epidermal Growth Factor Receptor (EGFR) Mutation Status

To determine EGFR mutation status in patients with advanced stage adenocarcinoma NSCLC. To determine the association between EGFR mutation status and demographic data in advanced stage ad...

Epidemiological and Scientific Evaluation of EGFR Mutation Status in Patients With Newly Diagnosed Locally Advanced or m

The primary objective of the study is to collect epidemiological data on EGFR mutation status (M+, M-) in a population of predominantly Caucasian ethnicity and to correlate EGFR mutation s...

HPV in Sentinel Lymph Nodes

This study examines sentinel lymph node tissue from early stage cervical cancer patients treated with radical hysterectomy and removal of pelvic sentinel lymph nodes (SLN). SLNs are tested...

Medical and Biotech [MESH] Definitions

A family of predominantly nuclear proteins that regulate gene transcription and protein degradation. The expansion of CAG trinucleotide repeats in genes that encode Ataxins is associated with SPINOCEREBELLAR ATAXIAS (SCA). In SCA patients, the number of CAG repeats correlates with the severity of disease and inversely correlates with the age of disease onset.

A dominantly-inherited ATAXIA first described in people of Azorean and Portuguese descent, and subsequently identified in Brazil, Japan, China, and Australia. This disorder is classified as one of the SPINOCEREBELLAR ATAXIAS (Type 3) and has been associated with a mutation of the MJD1 gene on chromosome 14. Clinical features include progressive ataxia, DYSARTHRIA, postural instability, nystagmus, eyelid retraction, and facial FASCICULATIONS. DYSTONIA is prominent in younger patients (referred to as Type I Machado-Joseph Disease). Type II features ataxia and ocular signs; Type III features MUSCULAR ATROPHY and a sensorimotor neuropathy; and Type IV features extrapyramidal signs combined with a sensorimotor neuropathy. (From Clin Neurosci 1995;3(1):17-22; Ann Neurol 1998 Mar;43(3):288-96)

A strain of mice arising from a spontaneous MUTATION (mdx) in inbred C57BL mice. This mutation is X chromosome-linked and produces viable homozygous animals that lack the muscle protein DYSTROPHIN, have high serum levels of muscle ENZYMES, and possess histological lesions similar to human MUSCULAR DYSTROPHY. The histological features, linkage, and map position of mdx make these mice a worthy animal model of DUCHENNE MUSCULAR DYSTROPHY.

A prolonged seizure or seizures repeated frequently enough to prevent recovery between episodes occurring over a period of 20-30 minutes. The most common subtype is generalized tonic-clonic status epilepticus, a potentially fatal condition associated with neuronal injury and respiratory and metabolic dysfunction. Nonconvulsive forms include petit mal status and complex partial status, which may manifest as behavioral disturbances. Simple partial status epilepticus consists of persistent motor, sensory, or autonomic seizures that do not impair cognition (see also EPILEPSIA PARTIALIS CONTINUA). Subclinical status epilepticus generally refers to seizures occurring in an unresponsive or comatose individual in the absence of overt signs of seizure activity. (From N Engl J Med 1998 Apr 2;338(14):970-6; Neurologia 1997 Dec;12 Suppl 6:25-30)

Mutation process that restores the wild-type PHENOTYPE in an organism possessing a mutationally altered GENOTYPE. The second "suppressor" mutation may be on a different gene, on the same gene but located at a distance from the site of the primary mutation, or in extrachromosomal genes (EXTRACHROMOSOMAL INHERITANCE).

Quick Search


DeepDyve research library

Searches Linking to this Article