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transcriptional responses to LDIR and HDIR. Our proposed method is based on identification of networks
of co-regulated biological processes under LDIR and HDIR. Our approach is based on the premise that
phenotypic differences are results of interworking/interweaving of biological processes instead of
individual genes and biological pathways. First, we identified dysregulated biological processes under
LDIR and HDIR separately. Then, we constructed a co-regulation matrix of biological process under the
two conditions. Based on this, we built an interaction network depicting co-regulation of these processes.
Finally, we sought for highly connected biological processes that are commonly and differentially
perturbed by LDIR and HDIR.
(PS2-04) Genetic analysis for predictors of distant metastatic disease in colorectal cancer using The
1;2
1;2
1;2
Cancer Genome Atlas. Daniel G. Tanenbaum ; William A. Hall, MD ; Lauren E. Colbert, BS ; Daniel Brat,
5;2
3;2
5;2
4;2
5;2
MD, PhD ; Jun Kong, PhD ; Sungjin Kim, MS ; Bhakti Dwivedi, PhD ; Jeanne Kowalski, PhD ; Jerome
1;2
Landry, MBA, MD ; and David S. Yu, MD, PhD, 1;2 Department of Radiation Oncology, Winship Cancer
1
2
3
Institute, Atlanta, GA ; Emory University, Atlanta, GA ; Department of Pathology, Atlanta, GA ; Center for
4
Comprehensive Informatics, Atlanta, GA ; and Winship Biostatistics and Bioinformatics Shared Resource,
Atlanta, GA
5
Purpose/Objectives: Clinical predictors for the development of distant metastatic disease in colorectal
cancer (CRC) are limited. Such clinical predictors could help to guide systemic and local treatment
strategies. We explored genetic alterations associated with distant metastatic disease in CRC using The
Cancer Genome Atlas (TCGA). Materials/Methods: Clinical characteristics and genetic sequencing data
were obtained from TCGA for all available patients with CRC. cBioPortal was used to ascertain genetic
alterations, defined as somatic mutations, deletions, or copy number alterations, with Mutation
Significance (Mutsig) q-value <0.05 and/or Genomic Identification of Significant Targets in Cancer (GISTIC)
q-value <0.05. Odds ratio with a 95% confidence interval and chi-square analysis or Fisher Exact Test were
used to determine the associated specific genetic alterations with distant metastases, microsatellite
instability (MSI), and lymph node (LN) involvement. Results: Two hundred twenty samples were available
with both sequencing and copy number analysis. Sixty-five samples were categorized as rectal primary
and 155 were colon primary. 52.3% of patients were male, median age at diagnosis was 69 years old, 33
patients had confirmed pathologic metastatic disease, and 86 patients had pathologic LN positive disease.
Distant metastases were associated with alteration in TNFRSF10C (4.26 [1.52-11.97]; p=0.0033) and DKK4
(3.49 [1.09-11.18]; p=0.0264). Absence of distant metastases was associated with alterations in ABCA12
(p=0.0498) and COL12A1 (p=0.0493). LN positivity was associated with alterations in TNFRSF10C (4.60
[1.58-13.40]; p=0.0033), but not with DKK4 (p=0.39), ABCA12 (p=0.10), or COL12A1 (p=0.13). MSI was not
associated with alterations in TNFRSF10C (p=0.66), DKK4 (p=0.23), ABCA12 (p=0.74), or COL12A1 (p=0.98).
Conclusions: Our initial exploratory analysis demonstrates specific genetic alterations in CRC may be
associated with distant metastasis. If successfully validated in an independent cohort, such genetic
profiles could be used clinically to support optimal systemic treatment strategies versus more aggressive
localized therapies in patients with CRC.
138 | P a g e
of co-regulated biological processes under LDIR and HDIR. Our approach is based on the premise that
phenotypic differences are results of interworking/interweaving of biological processes instead of
individual genes and biological pathways. First, we identified dysregulated biological processes under
LDIR and HDIR separately. Then, we constructed a co-regulation matrix of biological process under the
two conditions. Based on this, we built an interaction network depicting co-regulation of these processes.
Finally, we sought for highly connected biological processes that are commonly and differentially
perturbed by LDIR and HDIR.
(PS2-04) Genetic analysis for predictors of distant metastatic disease in colorectal cancer using The
1;2
1;2
1;2
Cancer Genome Atlas. Daniel G. Tanenbaum ; William A. Hall, MD ; Lauren E. Colbert, BS ; Daniel Brat,
5;2
3;2
5;2
4;2
5;2
MD, PhD ; Jun Kong, PhD ; Sungjin Kim, MS ; Bhakti Dwivedi, PhD ; Jeanne Kowalski, PhD ; Jerome
1;2
Landry, MBA, MD ; and David S. Yu, MD, PhD, 1;2 Department of Radiation Oncology, Winship Cancer
1
2
3
Institute, Atlanta, GA ; Emory University, Atlanta, GA ; Department of Pathology, Atlanta, GA ; Center for
4
Comprehensive Informatics, Atlanta, GA ; and Winship Biostatistics and Bioinformatics Shared Resource,
Atlanta, GA
5
Purpose/Objectives: Clinical predictors for the development of distant metastatic disease in colorectal
cancer (CRC) are limited. Such clinical predictors could help to guide systemic and local treatment
strategies. We explored genetic alterations associated with distant metastatic disease in CRC using The
Cancer Genome Atlas (TCGA). Materials/Methods: Clinical characteristics and genetic sequencing data
were obtained from TCGA for all available patients with CRC. cBioPortal was used to ascertain genetic
alterations, defined as somatic mutations, deletions, or copy number alterations, with Mutation
Significance (Mutsig) q-value <0.05 and/or Genomic Identification of Significant Targets in Cancer (GISTIC)
q-value <0.05. Odds ratio with a 95% confidence interval and chi-square analysis or Fisher Exact Test were
used to determine the associated specific genetic alterations with distant metastases, microsatellite
instability (MSI), and lymph node (LN) involvement. Results: Two hundred twenty samples were available
with both sequencing and copy number analysis. Sixty-five samples were categorized as rectal primary
and 155 were colon primary. 52.3% of patients were male, median age at diagnosis was 69 years old, 33
patients had confirmed pathologic metastatic disease, and 86 patients had pathologic LN positive disease.
Distant metastases were associated with alteration in TNFRSF10C (4.26 [1.52-11.97]; p=0.0033) and DKK4
(3.49 [1.09-11.18]; p=0.0264). Absence of distant metastases was associated with alterations in ABCA12
(p=0.0498) and COL12A1 (p=0.0493). LN positivity was associated with alterations in TNFRSF10C (4.60
[1.58-13.40]; p=0.0033), but not with DKK4 (p=0.39), ABCA12 (p=0.10), or COL12A1 (p=0.13). MSI was not
associated with alterations in TNFRSF10C (p=0.66), DKK4 (p=0.23), ABCA12 (p=0.74), or COL12A1 (p=0.98).
Conclusions: Our initial exploratory analysis demonstrates specific genetic alterations in CRC may be
associated with distant metastasis. If successfully validated in an independent cohort, such genetic
profiles could be used clinically to support optimal systemic treatment strategies versus more aggressive
localized therapies in patients with CRC.
138 | P a g e
