WBR0753

Author	[[PageAuthor::Yazan Daaboul, M.D. (Reviewed by Yazan Daaboul, M.D.)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Genetics
Sub Category	SubCategory::Musculoskeletal/Rheumatology
Prompt	[[Prompt::A 15-year-old boy is brought by his mother to the physician's office for right thigh pain. The child explains that the pain has been progressively worsening over the past 2 weeks and is now waking him at night. His mother adds that he has recently been having low-grade fevers and unintentional weight loss. Bone MRI and FDG-PET scan demonstrate a mass in the femoral diaphysis with no metastasis or lymph node involvement. Biopsy of the mass is shown in the image below. Molecular studies confirm a chromosomal translocation. Which of the following is the most likely molecular etiology of the patient's condition? ]]
Answer A	AnswerA::t(11,22)
Answer A Explanation	AnswerAExp::Ewing's sarcoma is characterized by a t(11,22) chromosomal translocation.
Answer B	AnswerB::t(8,14)
Answer B Explanation	AnswerBExp::t(8,14) translocation is associated with the development of Burkitt's lymphoma.
Answer C	AnswerC::t(15,17)
Answer C Explanation	AnswerCExp::t(15,17) translocation is associated with the development of M3 type of acute myelogenous leukemia (AML).
Answer D	AnswerD::t(12,21)
Answer D Explanation	AnswerDExp::t(12,21) translocation is a good prognostic factor among patients with acute lymphoblastic leukemia (ALL).
Answer E	AnswerE::t(11,14)
Answer E Explanation	AnswerEExp::t(11,14) is associated with the development of Mantle cell lymphoma.
Right Answer	RightAnswer::A
Explanation	[[Explanation::Ewing's sarcoma is the second most common bone tumor in children and adolescents. It is a malignant condition that is typically located in the diaphysis of the long bones. Ewing's sarcoma is part of Ewing's sarcoma family of tumors (ESFT), which includes several tumors: Ewing's sarcoma, Askin tumor, and peripheral primitive neuroectodermal tumor. Ewing's sarcoma has a high rate of rapid metastasis, but chemotherapy has greatly contributed to the survival of patients with Ewing's sarcoma. Before chemotherapy, only 10% of patients survived, but now the majority of patients with primary local tumors survive. Ewing's sarcoma is optimally diagnosed by biopsy of the mass, which typically demonstrates small round blue "onion" cells. Molecular findings in Ewing's sarcoma typically show a t(11,22) chromosomal translocation, which results in the formation of EWS-FL11 fusion gene. Normally, the EWS gene (chromosome 22) encodes an RNA-binding proteins, whereas FL11 gene (chromosome 11) encodes a protein with a DNA-binding domain. Educational Objective: Ewing's sarcoma is characterized by a t(11,22) chromosomal translocation that results in the formation of a EWS-FL11 fusion gene. References: Balamuth N, Womer RB. Ewing's sarcoma. Lancet Oncol. 2011; 11:184-92. Image Attribution: Ewing sarcoma - PAS - very high mag.jpg by user:Nephron on commons.wikimedia.org under the terms of the GNU Free Documentation License v1.2 licensed under the Creative Commons Attribution-Share Alike 3.0 Unported license. Retrieved on 6-March-2015. First Aid 2014 page 422]]
Approved	Approved::No
Keyword	WBRKeyword::Ewing's sarcoma, WBRKeyword::Childhood bone tumor, WBRKeyword::PNET, WBRKeyword::Bone tumor, WBRKeyword::Diaphysis, WBRKeyword::t(11, WBRKeyword::22) translocation, WBRKeyword::EWS, WBRKeyword::FL11, WBRKeyword::EWS-FL11, WBRKeyword::Fusion gene, WBRKeyword::Genetics, WBRKeyword::Genetic translocation
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