Gene amplification, or an increase in copy number of a confined region on the chromosome arm, has been identified as a critical genetic event that contributes to the development of various cancers. There is increased expression of certain genes within the amplified regions, which alters normal cell growth and survival pathways, and contributes to tumorigenesis. Although previous studies show that some regions are amplified in more than one cancer type, direct analyses comparing the size and gene composition of these amplified regions across tumor types have not been performed. In the current study, we used copy number and RNA sequencing data from our published data and The Cancer Genome Atlas (TCGA) to characterize the commonly affected 12q13-q14 and 12q15 chromosomal regions in rhabdomyosarcoma, glioblastoma multiforme, lung adenocarcinoma, and liposarcoma. Based on our analysis of copy number data from high-density single-nucleotide polymorphism arrays, we observed a 0.08 Mb common region of overlap of the 12q13-q14 amplicons and a 0.20 Mb common region of overlap of the 12q15 amplicons across these tumor types. Differential gene expression analysis between amplified and nonamplified samples showed that OS9, TSPAN31, CDK4, CYP27B1, METTL1, EEF1AKMT3, and TSFM were overexpressed by the 12q13-q14 amplicons. Similarly, MDM2 and CPM were overexpressed by the 12q15 chromosomal amplicons. In addition to the common region of overlap, regions of tumor-type specific amplification were also found in our analysis. The 12q13-q14 amplicon in fusion-positive rhabdomyosarcoma extended 0.48 Mb toward the centromere, while the 12q13-q14 amplicons in dedifferentiated liposarcoma and lung adenocarcinoma extended 0.56 Mb and 0.96 Mb, respectively, toward the telomere. For the 12q15 region, the amplicon in lung adenocarcinoma extended 1.3 Mb toward the centromere, while the amplicons in dedifferentiated liposarcoma and fusion-negative rhabdomyosarcoma extended 1.4 Mb and 1.6 Mb, respectively, toward the telomere. Gene expression analyses showed that some genes from these tumor-specific regions of amplification were preferentially overexpressed in the corresponding tumor types. For example, four genes from the fusion-positive rhabdomyosarcoma-specific 12q13-q14 amplicon (NEMP1, NAB2, SHMT2, and R3HDM2) and two genes from the lung adenocarcinoma-specific 12q15 amplicon (MDM1 and RAP1B) were specifically overexpressed in these two tumor types. Our findings indicate that, in addition to common regions of amplification across multiple tumor types, there are tumor-specific amplified regions and overexpressed genes that indicate the presence of unique features within each cancer category affecting these amplification events.

Citation Format: Prasantha L. Vemu, Gregory E. Hoy, Wenyue Sun, Jack Shern, Javed Khan, Frederic G. Barr. Comparing amplification of 12q13-q14 and 12q15 chromosomal regions across cancer types through genomic and transcriptome analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4357.