Abstract
Background: The weight that gene copy number plays in transcription remains controversial; although in specific cases gene expression correlates with copy number, the relationship cannot be inferred at the global level. We hypothesized that genes steadily expressed by 15 melanoma cell lines (CMs) and their parental tissues (TMs) should be critical for oncogenesis and their expression most frequently influenced by their respective copy number.Results: Functional interpretation of 3,030 transcripts concordantly expressed (Pearson's correlation coefficient p-value < 0.05) by CMs and TMs confirmed an enrichment of functions crucial to oncogenesis. Among them, 968 were expressed according to the transcriptional efficiency predicted by copy number analysis (Pearson's correlation coefficient p-value < 0.05). We named these genes, "genomic delegates" as they represent at the transcriptional level the genetic footprint of individual cancers. We then tested whether the genes could categorize 112 melanoma metastases. Two divergent phenotypes were observed: one with prevalent expression of cancer testis antigens, enhanced cyclin activity, WNT signaling, and a Th17 immune phenotype (Class A). This phenotype expressed, therefore, transcripts previously associated to more aggressive cancer. The second class (B) prevalently expressed genes associated with melanoma signaling including MITF, melanoma differentiation antigens, and displayed a Th1 immune phenotype associated with better prognosis and likelihood to respond to immunotherapy. An intermediate third class (C) was further identified. The three phenotypes were confirmed by unsupervised principal component analysis.Conclusions: This study suggests that clinically relevant phenotypes of melanoma can be retraced to stable oncogenic properties of cancer cells linked to their genetic back bone, and offers a roadmap for uncovering novel targets for tailored anti-cancer therapy.
| Original language | English |
|---|---|
| Article number | 156 |
| Journal | BMC Genomics |
| Volume | 13 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 26 Apr 2012 |
Fingerprint
Keywords
- Cancer
- Melanoma
- Melanoma genetics
- Tumor microenvironment
ASJC Scopus subject areas
- Biotechnology
- Genetics
Cite this
The stable traits of melanoma genetics : An alternate approach to target discovery. / Spivey, Tara L.; De Giorgi, Valeria; Zhao, Yingdong; Bedognetti, Davide; Pos, Zoltan; Liu, Qiuzhen; Tomei, Sara; Ascierto, Maria L.; Uccellini, Lorenzo; Reinboth, Jennifer; Chouchane, Lotfi; Stroncek, David F.; Wang, Ena; Marincola, Francesco M.
In: BMC Genomics, Vol. 13, No. 1, 156, 26.04.2012.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The stable traits of melanoma genetics
T2 - An alternate approach to target discovery
AU - Spivey, Tara L.
AU - De Giorgi, Valeria
AU - Zhao, Yingdong
AU - Bedognetti, Davide
AU - Pos, Zoltan
AU - Liu, Qiuzhen
AU - Tomei, Sara
AU - Ascierto, Maria L.
AU - Uccellini, Lorenzo
AU - Reinboth, Jennifer
AU - Chouchane, Lotfi
AU - Stroncek, David F.
AU - Wang, Ena
AU - Marincola, Francesco M.
PY - 2012/4/26
Y1 - 2012/4/26
N2 - Background: The weight that gene copy number plays in transcription remains controversial; although in specific cases gene expression correlates with copy number, the relationship cannot be inferred at the global level. We hypothesized that genes steadily expressed by 15 melanoma cell lines (CMs) and their parental tissues (TMs) should be critical for oncogenesis and their expression most frequently influenced by their respective copy number.Results: Functional interpretation of 3,030 transcripts concordantly expressed (Pearson's correlation coefficient p-value < 0.05) by CMs and TMs confirmed an enrichment of functions crucial to oncogenesis. Among them, 968 were expressed according to the transcriptional efficiency predicted by copy number analysis (Pearson's correlation coefficient p-value < 0.05). We named these genes, "genomic delegates" as they represent at the transcriptional level the genetic footprint of individual cancers. We then tested whether the genes could categorize 112 melanoma metastases. Two divergent phenotypes were observed: one with prevalent expression of cancer testis antigens, enhanced cyclin activity, WNT signaling, and a Th17 immune phenotype (Class A). This phenotype expressed, therefore, transcripts previously associated to more aggressive cancer. The second class (B) prevalently expressed genes associated with melanoma signaling including MITF, melanoma differentiation antigens, and displayed a Th1 immune phenotype associated with better prognosis and likelihood to respond to immunotherapy. An intermediate third class (C) was further identified. The three phenotypes were confirmed by unsupervised principal component analysis.Conclusions: This study suggests that clinically relevant phenotypes of melanoma can be retraced to stable oncogenic properties of cancer cells linked to their genetic back bone, and offers a roadmap for uncovering novel targets for tailored anti-cancer therapy.
AB - Background: The weight that gene copy number plays in transcription remains controversial; although in specific cases gene expression correlates with copy number, the relationship cannot be inferred at the global level. We hypothesized that genes steadily expressed by 15 melanoma cell lines (CMs) and their parental tissues (TMs) should be critical for oncogenesis and their expression most frequently influenced by their respective copy number.Results: Functional interpretation of 3,030 transcripts concordantly expressed (Pearson's correlation coefficient p-value < 0.05) by CMs and TMs confirmed an enrichment of functions crucial to oncogenesis. Among them, 968 were expressed according to the transcriptional efficiency predicted by copy number analysis (Pearson's correlation coefficient p-value < 0.05). We named these genes, "genomic delegates" as they represent at the transcriptional level the genetic footprint of individual cancers. We then tested whether the genes could categorize 112 melanoma metastases. Two divergent phenotypes were observed: one with prevalent expression of cancer testis antigens, enhanced cyclin activity, WNT signaling, and a Th17 immune phenotype (Class A). This phenotype expressed, therefore, transcripts previously associated to more aggressive cancer. The second class (B) prevalently expressed genes associated with melanoma signaling including MITF, melanoma differentiation antigens, and displayed a Th1 immune phenotype associated with better prognosis and likelihood to respond to immunotherapy. An intermediate third class (C) was further identified. The three phenotypes were confirmed by unsupervised principal component analysis.Conclusions: This study suggests that clinically relevant phenotypes of melanoma can be retraced to stable oncogenic properties of cancer cells linked to their genetic back bone, and offers a roadmap for uncovering novel targets for tailored anti-cancer therapy.
KW - Cancer
KW - Melanoma
KW - Melanoma genetics
KW - Tumor microenvironment
UR - http://www.scopus.com/inward/record.url?scp=84860110928&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84860110928&partnerID=8YFLogxK
U2 - 10.1186/1471-2164-13-156
DO - 10.1186/1471-2164-13-156
M3 - Article
C2 - 22537248
AN - SCOPUS:84860110928
VL - 13
JO - BMC Genomics
JF - BMC Genomics
SN - 1471-2164
IS - 1
M1 - 156
ER -