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2.  Ovarian sex cord -stromal tumors, pleuropulmonary blastoma and DICER1 mutations: A report from the International Pleuropulmonary blastoma Registry 
Gynecologic oncology  2011;122(2):246-250.
Objective
Pleuropulmonary blastoma (PPB) is a childhood cancer arising from pleuropulmonary mesenchyme. This neoplasm is a sentinel disease in a familial tumor syndrome recently found to be associated with germline mutations in DICER1. Observations of ovarian sex cord-stromal tumors (OSCST) in PPB kindreds led to further study. We sought to characterize ovarian tumors seen in probands and families with PPB and PPB-related conditions and define germline DICER1 status.
Methods
Patient and family records of pathology-reviewed PPB cases enrolled in the International PPB Registry (IPPBR) were searched for ovarian tumors. Ovarian tumor pathology specimens were obtained and centrally-reviewed. Germline DNA from patients with ovarian tumors was tested for DICER1 mutations. Three additional OSCST patients registered in the IPPBR were also tested for mutations in DICER1.
Results
Among 296 kindreds including 325 children with PPB, we observed 3 children with both PPB and Sertoli-Leydig cell tumors (SLCT)/Sertoli cell tumors. Among family members of PPB patients, we identified 6 OSCST (3 SLCT, 1 Sertoli cell tumor, 1 juvenile granulosa cell tumor, 1 gynandroblastoma). Age at ovarian tumor diagnosis was youngest in PPB probands and younger in family members than in OSCST in general. Germline DICER1 mutations were identified in 4 of 6 patients with OSCST from PPB kindreds and in 2 of 3 children with OSCST and no personal or family history of PPB.
Conclusions
Primary ovarian neoplasms, particularly OSCST, are a manifestation of the familial PPB syndrome and may be the initial clinical presentation of DICER1 mutations within a family.
doi:10.1016/j.ygyno.2011.03.024
PMCID: PMC3138876  PMID: 21501861
sex cord-stromal tumors; ovary; cancer; DICER1
3.  Health and Risk Behaviors in Survivors of Childhood Acute Myeloid Leukemia: A Report From the Children’s Oncology Group 
Pediatric blood & cancer  2010;55(1):157-164.
Background
Survivors of childhood acute myeloid leukemia (AML) face increased risks of chronic disease and secondary malignancies. Substance exposure may compound these risks.
Procedures
Participants were diagnosed with AML at <21 years of age and survived ≥5 years following diagnosis. All underwent chemotherapy alone or followed by autologous BMT (chemo ± autoBMT) or underwent allogeneic BMT (alloBMT) if an HLA-matched related donor was available. Survivors completed a health questionnaire and a Youth Risk Behavior Survey (YRBS).
Results
Of eligible survivors, 117 were ≥18 years of age and completed a YRBS. Survivors were a mean age of 10 years at diagnosis and 24 years at interview. Of the substance exposures assessed by YRBS, tobacco, alcohol, and marijuana were most common. Twenty-two percent (22%) had smoked cigarettes in the last 30 days. One-quarter (25%) reported binge drinking in the last month. None of these exposures varied by treatment group. Less than 10% of survivors reported cocaine, heroin, or methamphetamine use. Men were more likely to report high substance exposure (P = 0.004). Sadness/suicidality score was associated with cancer-related anxiety (P = 0.006) and multiple health conditions (P = 0.006).
Conclusions
This analysis reveals exposure to tobacco, alcohol, and marijuana in young adults with few differences based on treatment received. Survivors with cancer-related anxiety or multiple health conditions were more likely to report sadness/hopelessness.
doi:10.1002/pbc.22443
PMCID: PMC3152207  PMID: 20232426
leukemia; pediatric; smoking; survivor
4.  Nasal chondromesenchymal hamartomas arise secondary to germline and somatic mutations of DICER1 in the pleuropulmonary blastoma tumor-predisposition disorder 
Human genetics  2014;133(11):1443-1450.
Background
Nasal chondromesenchymal hamartoma (NCMH) is a rare nasal tumor that typically presents in young children. We previously reported on NCMH occurrence in children with pleuropulmonary blastoma (PPB), a rare pulmonary dysembryonic sarcoma that is the hallmark neoplasm in the PPB-associated DICER1 tumor predisposition disorder.
Methods
Original pathologic materials from individuals with a PPB, PPB-associated tumor and/or a DICER1 mutation were centrally reviewed by the International PPB Registry. Paraffin-embedded NCMH tumor tissue was available in three cases. Laser-capture microdissection was used to isolate mesenchymal spindle cells and cartilage in one case for Sanger sequencing of DICER1.
Results
Nine patients (5F/4M) had PPB and NCMH. NCMH was diagnosed at a median age of 10 years (range 6-21years). NCMH developed 4.5 - 13 years after PPB. Presenting NCMH symptoms included chronic sinusitis and nasal congestion. Five patients had bilateral tumors. Local NCMH recurrences required several surgical resections in two patients, but all nine patients were alive at 0 – 16 years of follow-up. Pathogenic germline DICER1 mutations were found in 6/8 NCMH patients tested. In 2 of the patients with germline DICER1 mutations, somatic DICER1 missense mutations were also identified in their NCMH (E1813D; n=2). Three additional PPB patients developed other nasal lesions seen in the general population (a Schneiderian papilloma, chronic sinusitis with cysts, and allergic nasal polyps with eosinophils). Two of these patients had germline DICER1 mutations.
Conclusion
Pathogenic germline and somatic mutations of DICER1 in NCMH establishes that the genetic etiology of NCMH is similar to PPB, despite the disparate biological potential of these neoplasms.
doi:10.1007/s00439-014-1474-9
PMCID: PMC4185226  PMID: 25118636
Nasal chondromesenchymal hamartoma; DICER1; Pleuropulmonary blastoma

Results 1-4 (4)