The stable traits of melanoma genetics: An alternate approach to target discovery

Tara L. Spivey, Valeria De Giorgi, Yingdong Zhao, Davide Bedognetti, Zoltan Pos, Qiuzhen Liu, Sara Tomei, Maria L. Ascierto, Lorenzo Uccellini, Jennifer Reinboth, Lotfi Chouchane, David F. Stroncek, Ena Wang, Francesco M. Marincola

Research output: Contribution to journalArticle

25 Citations (Scopus)

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 languageEnglish
Article number156
JournalBMC Genomics
Volume13
Issue number1
DOIs
Publication statusPublished - 26 Apr 2012

Fingerprint

Melanoma
Phenotype
Genes
Neoplasms
Carcinogenesis
Melanoma-Specific Antigens
Cyclins
Gene Dosage
Differentiation Antigens
Testicular Neoplasms
Principal Component Analysis
Immunotherapy
Neoplasm Metastasis
Gene Expression
Antigens
Weights and Measures
Bone and Bones
Cell Line
Therapeutics

Keywords

  • Cancer
  • Melanoma
  • Melanoma genetics
  • Tumor microenvironment

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

Cite this

Spivey, T. L., De Giorgi, V., Zhao, Y., Bedognetti, D., Pos, Z., Liu, Q., ... Marincola, F. M. (2012). The stable traits of melanoma genetics: An alternate approach to target discovery. BMC Genomics, 13(1), [156]. https://doi.org/10.1186/1471-2164-13-156

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 journalArticle

Spivey, TL, De Giorgi, V, Zhao, Y, Bedognetti, D, Pos, Z, Liu, Q, Tomei, S, Ascierto, ML, Uccellini, L, Reinboth, J, Chouchane, L, Stroncek, DF, Wang, E & Marincola, FM 2012, 'The stable traits of melanoma genetics: An alternate approach to target discovery', BMC Genomics, vol. 13, no. 1, 156. https://doi.org/10.1186/1471-2164-13-156
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. / The stable traits of melanoma genetics : An alternate approach to target discovery. In: BMC Genomics. 2012 ; Vol. 13, No. 1.
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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.",
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AU - Liu, Qiuzhen

AU - Tomei, Sara

AU - Ascierto, Maria L.

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AU - Reinboth, Jennifer

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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.

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