[1910] DNA Copy Number Analysis and Gene Expression Profiles in Abdominal Malignant Mesothelioma (AMM)

AN Sireci, B Levy, RN Taub, JL Chen, O Nahum, AC Borczuk. Columbia University Medical Center, New York, NY

Background: AMM is a neoplasm of the abdominal serosa with two distinct prognostic subgroups. We describe recurrent genetic abnormalities in this tumor type and identify five that correlate with prognosis.
Design: Gene expression (GE) profiling (Affymetrix U133 Plus2 array) was performed on laser capture microdissected AMM from 14 patients (7 favorable prognosis and 7 poor prognosis, as defined by survival at 1000 days). Needle-dissected tumor from 13 of these patients was studied for copy number (CN) alteration (Affymetrix SNParray 6.0). GE and CN data were analyzed using Partek software. A list of CN alterations present in >35% of tumors, regardless of prognosis, was compiled. Genes with significant CN-GE correlations that predicted prognosis were identified.
Results: A list of 19 genes that exhibited CN variation in >35% of tumors is summarized in table 1 by chromosomal region. BAP1, a known BRCA1-associated tumor suppressor gene, was lost in 5 of 13 tumors. A region of genomic loss in 6/13 cases on 22q11.1 contained BCL2-like13 and BID, two genes with pro-apoptotic functions. Five genes for which CN analysis correlated significantly with GE and that clustered by prognosis were identified. DENND1B, gained in 3/6 poor prognosis tumors and 0/7 of good prognosis tumors is a known anti-apoptotic protein. Additionally, LAMC1, a laminin family member, was gained in 4/6 poor prognosis tumors and remained unchanged in all good prognosis tumors. Over-expression of laminins has been shown in aggressive gliomas.

Table 1: Recurrent CN Losses in 13 AMM

Chromosomal cytoband	Location	# of genes in region	# abnormal	Loss or gain
1q21.3	150.837000 to 150.853200	2 (Lep14, Lep15)	6	Loss
3p21.1	52.3 to 52.6	10 (BAP1, PBRM1)	5	Loss
22q11.1	15.420 to 16.890	19 (BCL2-L13, BID)	6	Loss
22q12.1	26.565 to 26.776	1 (sez6l)	7	Loss
22q21.23	22.655 to 22.727	4 (GSTT1)	5	Loss

Conclusions: We have identified 19 recurrent CN alterations in AMM. Additionally, five genes with copy number variations that correlated with GE and that predicted prognosis were found. Four of these have been implicated in other malignancies.
Category: Pan-genomic/Pan-proteomic Approaches to Diseases

Monday, March 22, 2010 1:00 PM

Poster Session II # 222, Monday Afternoon