title: Mutational profiling of acute lymphoblastic leukemia with testicular relapse.
abstract: Relapsed acute lymphoblastic leukemia (ALL) is the leading cause of deaths of childhood cancer. Although relapse usually happens in the bone marrow, extramedullary relapse occasionally occurs including either the central nervous system or testis (<1-2%). We selected two pediatric ALL patients who experienced testicular relapse and interrogated their leukemic cells with exome sequencing. The sequencing results and clonality analyses suggest that relapse of patient D483 directly evolved from the leukemic clone at diagnosis which survived chemotherapy. In contrast, relapse leukemia cells (both bone marrow and testis) of patient D727 were likely derived from a common ancestral clone, and testicular relapse likely arose independently from the bone marrow relapsed leukemia. Our findings decipher the mutational spectra and shed light on the clonal evolution of two cases of pediatric ALL with testicular relapse. Presence of CREBBP/NT5C2 mutations suggests that a personalized therapeutic approach should be applied to these two patients.
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore. csidlw@nus.edu.sg.
authors.forename: Ling-Wen
authors.initials: LW
authors.lastname: Ding
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
authors.forename: Qiao-Yang
authors.initials: QY
authors.lastname: Sun
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
authors.forename: Anand
authors.initials: A
authors.lastname: Mayakonda
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
authors.forename: Kar-Tong
authors.initials: KT
authors.lastname: Tan
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.|Division of Hematology/Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, USA.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Chien
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.|Division of Hematology/Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, USA.
authors.forename: De-Chen
authors.initials: DC
authors.lastname: Lin
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
authors.forename: Yan-Yi
authors.initials: YY
authors.lastname: Jiang
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
authors.forename: Liang
authors.initials: L
authors.lastname: Xu
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.|Department of Medical Oncology and Clinical Research, Cancer Institute (WIA), Adyar Chennai, India.
authors.forename: Manoj
authors.initials: M
authors.lastname: Garg
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.|Department of Haematology, Singapore General Hospital, Singapore, Singapore.
authors.forename: Zhen-Tang
authors.initials: ZT
authors.lastname: Lao
authors.affiliation: Division of Hematology/Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Lill
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
authors.forename: Henry
authors.initials: H
authors.lastname: Yang
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore. allen_yeoh@nuhs.edu.sg.|Department of Pediatrics, Division of Hematology and Oncology, National University Health System, Singapore, Singapore. allen_yeoh@nuhs.edu.sg.
authors.forename: Allen Eng Juh
authors.initials: AE
authors.lastname: Yeoh
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.|Division of Hematology/Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, USA.
authors.forename: H Phillip
authors.initials: HP
authors.lastname: Koeffler
mesh_terms: D002675:Child, Preschool; D060965:Clonal Evolution / Q000235:genetics; D004252:DNA Mutational Analysis; D006801:Humans; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000473:pathology*; D012008:Recurrence; D013736:Testicular Neoplasms / Q000235:genetics / Q000473:pathology / Q000556:secondary*
keywords: ALL; Acute lymphoblastic leukemia; Extramedullary relapse; Testicular relapse