125. Expect the unexpected? Microarray analyses of pediatric tumors

Aly Abdelkareem

Maxine Sutcliffe

Dr Maxine Sutcliffe has been the Director of Cytogenetics and Molecular Cytogenetics at Johns Hopkins All Children’s Hospital in St. Petersburg, FL for more than 30 years.  She is also an Emeritus Associate Professor of Pediatrics at University of South Florida, Tampa, FL.

Genetics has always been her focus: BSc (Genetics), PhD (Developmental Genetics), both from London University (London, England); Fellowship in Molecular Genetics, St Mary’s Hospital Medical School, London and subsequently dual Fellowship in Cytogenetics and Molecular Genetics at the ABMGG accredited Regional Genetics Program, USF.  She is also a Cytogenetics diplomate of the Canadian College of Medial Geneticists and a Founding Fellow of ACMGG.

Dr Sutcliffe has taught genetics at all levels: Medical School USF, Genetic Counseling program USF, genetics curriculum/examination committees at USF and the State of Florida and as PI for FL State Cytogenetics Technologist training program.  She has led her Laboratory’s participation in POG, subsequently COG, since 1997.

She has published in numerous journals, cited in over 60 publications, two books, been invited to speak at universities, conferences and seminars across the US and UK, has been featured in three Discovery Channel programs and served as a professional expert on medical updates on Tampa Bay TV news channel. She remains passionate and committed to her chosen field and has special interest in pediatric cancer; both hematology and the solid tumors prevalent in children.

Dr Sutcliffe has been associated with CGC since the inaugural meeting in 2009; this is her twelfth CGC meeting attendance.


Maxine Sutcliffea, Ashley Robinsonb, Stephanie Smithb, Rodolfo Ortegab, Sara Gellatlyb

aJohns Hopkins All Children’s Hospital/University of South FL, Clearwater, FL, USA; bJohns Hopkins All Children’s Hospital, St Petersburg, FL, USA

Unusual, potentially important, findings are encountered when tumor genomic analysis uses a whole genome screening approach, illustrated in several cases presented.

Pilocytic astrocytomas are readily detectable by HD/SNP microarray, ~2Mb 7q34 tandem duplication resulting in fusions containing 5′ KIAA1549 and several 3′ exons of BRAF. These are not observed in higher grade astrocytomas. Array/cytogenetic analyses of an astrocytoma is presented that demonstrated was fusion-negative hyperdiploidy, amplification of 7q and an 86Kb intragenic Exon 1-8 deletion within BRAF.

A liver mass demonstrating a 1.78Mb 12q21-q22 deletion by array included the BTG1 gene. BTG1, originally a CMYC translocation partner in hematopoietic CLL, is an anti-proliferative gene constitutively expressed in quiescent cells, down-regulated during G0/G1 cell cycle. BTG1 is now described in various solid tumors including initiation/progression of hepatocellular carcinogenesis. Decreased BTG1 expression is hypothesized as a mechanism in HCC lacking mutations or promoter hypermethylation.

Osteosarcomas show multiple, complex abnormalities with high heterogeneity but fewer alterations characterize osteoblastomas. A distinct, unusual chromothripsis (compared to random change) showing a profile of continuous, repetitive segmental gain involving chromosome 14 was observed in osteoblastoma. Significantly, one gain within 14q24.3 involved the FOS transcription factor oncogene associated with bone tumor pathogenesis. The FOS gene family with transcription-factor complex AP-1, are implicated in cell proliferation, differentiation and transformation. Exploiting FOS alterations are suggested as diagnostic markers for osteoblastoma/ osteoid osteoma.

These analyses serve to highlight the capability of arrays, the ability to reveal potentially important results and information for tumorigenesis interpretation.