Prognostic impact of array-based genomic profiles in esophageal squamous cell cancer.
BACKGROUND
Esophageal squamous cell carcinoma (ESCC) is a genetically complex tumor type and a major cause of cancer related mortality. Although distinct genetic alterations have been linked to ESCC development and prognosis, the genetic alterations have not gained clinical applicability. We applied array-based comparative genomic hybridization (aCGH) to obtain a whole genome copy number profile relevant for identifying deranged pathways and clinically applicable markers.


METHODS
A 32 k aCGH platform was used for high resolution mapping of copy number changes in 30 stage I-IV ESCC. Potential interdependent alterations and deranged pathways were identified and copy number changes were correlated to stage, differentiation and survival.


RESULTS
Copy number alterations affected median 19% of the genome and included recurrent gains of chromosome regions 5p, 7p, 7q, 8q, 10q, 11q, 12p, 14q, 16p, 17p, 19p, 19q, and 20q and losses of 3p, 5q, 8p, 9p and 11q. High-level amplifications were observed in 30 regions and recurrently involved 7p11 (EGFR), 11q13 (MYEOV, CCND1, FGF4, FGF3, PPFIA, FAD, TMEM16A, CTTS and SHANK2) and 11q22 (PDFG). Gain of 7p22.3 predicted nodal metastases and gains of 1p36.32 and 19p13.3 independently predicted poor survival in multivariate analysis.


CONCLUSIONS
aCGH profiling verified genetic complexity in ESCC and herein identified imbalances of multiple central tumorigenic pathways. Distinct gains correlate with clinicopathological variables and independently predict survival, suggesting clinical applicability of genomic profiling in ESCC.
Carneiro
Ana
A
Department of Oncology, Lund University Hospital, 221 85 Lund, Sweden. Ana.Carneiro@med.lu.se
Isinger
Anna
A
Karlsson
Anna
A
Johansson
Jan
J
Jönsson
Göran
G
Bendahl
Pär-Ola
PO
Falkenback
Dan
D
Halvarsson
Britta
B
Nilbert
Mef
M
D000368:Aged; D004938:Esophageal Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008875:Middle Aged; D018307:Neoplasms, Squamous Cell / Q000175:diagnosis* / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D011379:Prognosis
D005819:Genetic Markers