Elucidating the Genetic Basis of the Pleuropulmonary Blastoma (PPB) Familial Cancer Syndrome

NCT00565903 | Completed

• 1 other identifier: 05-0192 / 201012830
• Study Type: observational
• Target: 1,247
• Locations: 1 country
• Sites: 1

Brief Summary

Pleuropulmonary Blastoma (PPB) is a rare lung tumor which develops in childhood. The underlying genetic factors which contribute to the development and progression of PPB are not defined. We are working to identify the genetic factors which may contribute to the development of this rare tumor.

Conditions

Pleuropulmonary Blastoma; Cystic Nephroma; Sertoli-Leydig Cell Tumor of Ovary; Medulloepithelioma; Embryonal Rhabdomyosarcoma of Cervix; Goiter; Sarcoma; Pineoblastoma; Pituitary Tumors; Wilms Tumor

Keywords

pleuropulmonary blastoma; PPB; cystic nephroma; DICER1; miRNA

Outcome Measures

Primary Outcomes (1)

• Identify the genetic factors which contribute to the development or progression of pleuropulmonary blastoma

  10 years

Secondary Outcomes (1)

• Define the clinical features of the pleuropulmonary blastoma (PPB) familial cancer syndrome.

  10 years

Eligibility Criteria

• Age: 1 Day - 95 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Families who have a child or adult with pleuropulmonary blastoma or cystic nephroma are invited to participate.

You may qualify if:

• Child or adult diagnosed with pleuropulmonary blastoma, cystic nephroma, embryonal rhabdomyosarcoma of uterine cervix, ovarian Sertoli-Leydig tumor or gynandroblastoma, pineoblastoma, pituitary blastoma, nasal chondromesenchymal hamartoma, medulloepithelioma, Wilms tumor, germline or mosaic DICER1 mutation

Sponsors & Collaborators

• Ashley Hill: lead

Study Sites (1)

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Related Publications (14)

• Schultz KAP, Williams GM, Kamihara J, Stewart DR, Harris AK, Bauer AJ, Turner J, Shah R, Schneider K, Schneider KW, Carr AG, Harney LA, Baldinger S, Frazier AL, Orbach D, Schneider DT, Malkin D, Dehner LP, Messinger YH, Hill DA. DICER1 and Associated Conditions: Identification of At-risk Individuals and Recommended Surveillance Strategies. Clin Cancer Res. 2018 May 15;24(10):2251-2261. doi: 10.1158/1078-0432.CCR-17-3089. Epub 2018 Jan 17.

  PMID: 29343557 RESULT

• Schultz KAP, Harris AK, Finch M, Dehner LP, Brown JB, Gershenson DM, Young RH, Field A, Yu W, Turner J, Cost NG, Schneider DT, Stewart DR, Frazier AL, Messinger Y, Hill DA. DICER1-related Sertoli-Leydig cell tumor and gynandroblastoma: Clinical and genetic findings from the International Ovarian and Testicular Stromal Tumor Registry. Gynecol Oncol. 2017 Dec;147(3):521-527. doi: 10.1016/j.ygyno.2017.09.034. Epub 2017 Oct 14.

  PMID: 29037807 RESULT

• Hill DA, Ivanovich J, Priest JR, Gurnett CA, Dehner LP, Desruisseau D, Jarzembowski JA, Wikenheiser-Brokamp KA, Suarez BK, Whelan AJ, Williams G, Bracamontes D, Messinger Y, Goodfellow PJ. DICER1 mutations in familial pleuropulmonary blastoma. Science. 2009 Aug 21;325(5943):965. doi: 10.1126/science.1174334. Epub 2009 Jun 25.

  PMID: 19556464 RESULT

• Pugh TJ, Yu W, Yang J, Field AL, Ambrogio L, Carter SL, Cibulskis K, Giannikopoulos P, Kiezun A, Kim J, McKenna A, Nickerson E, Getz G, Hoffher S, Messinger YH, Dehner LP, Roberts CW, Rodriguez-Galindo C, Williams GM, Rossi CT, Meyerson M, Hill DA. Exome sequencing of pleuropulmonary blastoma reveals frequent biallelic loss of TP53 and two hits in DICER1 resulting in retention of 5p-derived miRNA hairpin loop sequences. Oncogene. 2014 Nov 6;33(45):5295-302. doi: 10.1038/onc.2014.150. Epub 2014 Jun 9.

  PMID: 24909177 RESULT

• Schultz KA, Harris A, Williams GM, Baldinger S, Doros L, Valusek P, Frazier AL, Dehner LP, Messinger Y, Hill DA. Judicious DICER1 testing and surveillance imaging facilitates early diagnosis and cure of pleuropulmonary blastoma. Pediatr Blood Cancer. 2014 Sep;61(9):1695-7. doi: 10.1002/pbc.25092. Epub 2014 May 13.

  PMID: 24821309 RESULT

• Doros LA, Rossi CT, Yang J, Field A, Williams GM, Messinger Y, Cajaiba MM, Perlman EJ, A Schultz K, Cathro HP, Legallo RD, LaFortune KA, Chikwava KR, Faria P, Geller JI, Dome JS, Mullen EA, Gratias EJ, Dehner LP, Hill DA. DICER1 mutations in childhood cystic nephroma and its relationship to DICER1-renal sarcoma. Mod Pathol. 2014 Sep;27(9):1267-80. doi: 10.1038/modpathol.2013.242. Epub 2014 Jan 31.

  PMID: 24481001 RESULT

• Stewart DR, Messinger Y, Williams GM, Yang J, Field A, Schultz KA, Harney LA, Doros LA, Dehner LP, Hill DA. Nasal chondromesenchymal hamartomas arise secondary to germline and somatic mutations of DICER1 in the pleuropulmonary blastoma tumor predisposition disorder. Hum Genet. 2014 Nov;133(11):1443-50. doi: 10.1007/s00439-014-1474-9. Epub 2014 Aug 14.

  PMID: 25118636 RESULT

• Schultz KA, Yang J, Doros L, Williams GM, Harris A, Stewart DR, Messinger Y, Field A, Dehner LP, Hill DA. DICER1-pleuropulmonary blastoma familial tumor predisposition syndrome: a unique constellation of neoplastic conditions. Pathol Case Rev. 2014 Mar;19(2):90-100. doi: 10.1097/PCR.0000000000000027.

  PMID: 25356068 RESULT

• Messinger YH, Stewart DR, Priest JR, Williams GM, Harris AK, Schultz KA, Yang J, Doros L, Rosenberg PS, Hill DA, Dehner LP. Pleuropulmonary blastoma: a report on 350 central pathology-confirmed pleuropulmonary blastoma cases by the International Pleuropulmonary Blastoma Registry. Cancer. 2015 Jan 15;121(2):276-85. doi: 10.1002/cncr.29032. Epub 2014 Sep 10.

  PMID: 25209242 RESULT

• Rutter MM, Jha P, Schultz KA, Sheil A, Harris AK, Bauer AJ, Field AL, Geller J, Hill DA. DICER1 Mutations and Differentiated Thyroid Carcinoma: Evidence of a Direct Association. J Clin Endocrinol Metab. 2016 Jan;101(1):1-5. doi: 10.1210/jc.2015-2169. Epub 2015 Nov 10.

  PMID: 26555935 RESULT

• Khan NE, Bauer AJ, Schultz KAP, Doros L, Decastro RM, Ling A, Lodish MB, Harney LA, Kase RG, Carr AG, Rossi CT, Field A, Harris AK, Williams GM, Dehner LP, Messinger YH, Hill DA, Stewart DR. Quantification of Thyroid Cancer and Multinodular Goiter Risk in the DICER1 Syndrome: A Family-Based Cohort Study. J Clin Endocrinol Metab. 2017 May 1;102(5):1614-1622. doi: 10.1210/jc.2016-2954.

  PMID: 28323992 RESULT

• Kim J, Field A, Schultz KAP, Hill DA, Stewart DR. The prevalence of DICER1 pathogenic variation in population databases. Int J Cancer. 2017 Nov 15;141(10):2030-2036. doi: 10.1002/ijc.30907. Epub 2017 Aug 21.

  PMID: 28748527 RESULT

• Schultz KAP, Stewart DR, Kamihara J, Bauer AJ, Merideth MA, Stratton P, Huryn LA, Harris AK, Doros L, Field A, Carr AG, Dehner LP, Messinger Y, Hill DA. DICER1 Tumor Predisposition. 2014 Apr 24 [updated 2020 Apr 30]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK196157/

  PMID: 24761742 RESULT

• Brenneman M, Field A, Yang J, Williams G, Doros L, Rossi C, Schultz KA, Rosenberg A, Ivanovich J, Turner J, Gordish-Dressman H, Stewart D, Yu W, Harris A, Schoettler P, Goodfellow P, Dehner L, Messinger Y, Hill DA. Temporal order of RNase IIIb and loss-of-function mutations during development determines phenotype in pleuropulmonary blastoma / DICER1 syndrome: a unique variant of the two-hit tumor suppression model. F1000Res. 2015 Jul 10;4:214. doi: 10.12688/f1000research.6746.2. eCollection 2015.

  PMID: 26925222 RESULT

Related Links

• PPB Research Program website

Biospecimen

Retention: SAMPLES WITH DNA

We are collecting blood samples or saliva samples. When available, we also collect tumor samples from prior surgical procedures.

MeSH Terms

Conditions

Pleuropulmonary blastoma; Sertoli-Leydig Cell Tumor; Neuroectodermal Tumors, Primitive; Goiter; Sarcoma; Pinealoma; Pituitary Neoplasms; Wilms Tumor

Condition Hierarchy (Ancestors)

Sex Cord-Gonadal Stromal Tumors; Neoplasms, Gonadal Tissue; Neoplasms by Histologic Type; Neoplasms; Ovarian Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Testicular Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Genital Diseases; Genital Diseases, Male; Male Urogenital Diseases; Endocrine System Diseases; Gonadal Disorders; Testicular Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Thyroid Diseases; Neoplasms, Connective and Soft Tissue; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypothalamic Neoplasms; Supratentorial Neoplasms; Hypothalamic Diseases; Pituitary Diseases; Neoplasms, Complex and Mixed; Kidney Neoplasms; Urologic Neoplasms; Neoplastic Syndromes, Hereditary; Kidney Diseases; Urologic Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• D. Ashley Hill, MD

  Children's National Research Institute

  STUDY CHAIR

• Kris Ann Schultz, MD

  Children's Hospital and Clinics of Minnesota

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: FAMILY BASED
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, Professor of Pathology

Study Record Dates

• First Submitted: November 29, 2007
• First Posted: November 30, 2007
• Study Start: March 1, 2005
• Primary Completion: December 31, 2018
• Study Completion: December 31, 2022
• Last Updated: March 1, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share

Locations

US (1)