Abstract

PURPOSE
Molecular events underlying progression of well-differentiated liposarcoma (WDLS) to dedifferentiated liposarcoma (DDLS) are poorly defined. This study sought to identify copy number alterations (CNA) associated with dedifferentiation of WDLS, with DDLS morphology, and with patient outcomes.
EXPERIMENTAL DESIGN
Fifty-five WDLS and 52 DDLS were analyzed using Agilent 244K comparative genomic hybridization and Affymetrix U133A expression arrays. CNAs were identified by RAE analysis. Thirty-nine of the DDLS specimens were categorized morphologically by a single pathologist.
RESULTS
Nine regions of CNA were identified as recurrent in DDLS but not WDLS; 79% of DDLS had at least one of these CNAs. Loss of the chromosome segment 11q23-24, the most common event, was observed only in DDLS that morphologically resembled the genomically complex sarcomas, undifferentiated pleomorphic sarcoma and myxofibrosarcoma. 11q23-24 loss was itself associated with increased genomic complexity in DDLS. Loss of 19q13, but not 11q23-24, was associated with poor prognosis. Median disease-specific survival was shorter for patients with19q13 loss (27 months) than for patients with diploid 19q13 (>90 months; P < 0.0025), and 19q13 loss was associated with local recurrence (HR, 2.86; P = 0.013). Common copy number losses were associated with transcriptional downregulation of potential tumor suppressors and adipogenesis-related genes (e.g., EI24 and CEBPA).
CONCLUSIONS
Dedifferentiation of WDLS is associated with recurrent CNAs in 79% of tumors. In DDLS, loss of 11q23-24 is associated with genomic complexity and distinct morphology whereas loss of 19q13 predicts poor prognosis. CNAs in liposarcoma improve risk stratification for patients and will help identify potential tumor suppressors driving liposarcoma progression.

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Publisher Full Text

Authors

Crago AM, Socci ND, DeCarolis P, O'Connor R, Taylor BS, Qin LX, Antonescu CR, Singer S

Institution

Sarcoma Disease Management Program, Department of Surgery, Bioinformatics Core, Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.

Source

Clinical cancer research : an official journal of the American Association for Cancer Research 18:5 2012 Mar 1 pg 1334-40

MeSH

Adult
Aged
Aged, 80 and over
Chromosomes, Human, Pair 11
Chromosomes, Human, Pair 19
DNA Copy Number Variations
Disease Progression
Female
Genes, Tumor Suppressor
Genomic Instability
Humans
Liposarcoma
Male
Middle Aged
Prognosis
Risk Factors
Survival Analysis
Young Adult

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22241790