{"id":2301,"date":"2025-09-30T10:27:21","date_gmt":"2025-09-30T10:27:21","guid":{"rendered":"https:\/\/staging.irccs.com\/?post_type=laboratory&p=2301"},"modified":"2025-11-11T17:18:14","modified_gmt":"2025-11-11T17:18:14","slug":"genomic-architecture-of-cancer","status":"publish","type":"laboratory","link":"https:\/\/irccs.com\/it\/laboratori\/genomic-architecture-of-cancer\/","title":{"rendered":"GENOMIC ARCHITECTURE OF CANCER"},"content":{"rendered":"\n

<\/span>Research topic<\/h2>\n\n\n\n

Chromatin structure and epigenetic mechanisms for cancer growth and resistance to therapy.<\/p>\n\n\n\n

<\/span>Background<\/h2>\n\n\n\n

Recent advances in sequencing technologies and gene editing have revealed that cancer aggressiveness and resistance to standard treatments are strongly influenced by epigenetic factors, which regulate gene expression beyond the DNA sequence itself.<\/p>\n\n\n\n

Among epigenetic factors, the three-dimensional structure of the chromatin plays a prominent role. Chromatin conformation is a strictly regulated process that governs accessibility to the underlying DNA sequence and thereby guides cellular processes critical for maintaining cellular identity and function. Other than regulating the expression of oncogenes and tumor suppressors, chromatin architecture is instructing many cancer-associated phenotypes, such as metastasis, therapy resistance, and immune evasion.<\/p>\n\n\n\n

<\/span>Research achievements<\/h2>\n\n\n\n

The projects in our lab aim to understand the epigenetic mechanisms that determine cancer behavior, with a particular focus on chromatin alterations during cancer development and resistance to therapy.
We have initially analyzed these aspects in the context of pediatric acute T lymphoblastic leukemia (T-ALL), where we demonstrated that chromatin architecture is subverted when a normal T cell progenitor is transformed into a leukemic blast. This is often accompanied by the disruption of boundary elements that favor the \u201crewiring\u201d of the normal promoter-enhancer interactions, thus causing the promoters of proto-oncogenes to become activated by distal enhancers. A genome-wide characterization of chromatin architecture rearrangements across several patient groups has shown that specific conformations correspond to more aggressive subtypes, which in turn associate with increased resistance to therapy. We are now aiming at expanding these observations beyond pediatric leukemia, since we believe that similar mechanisms will apply to virtually every type of cancer.<\/p>\n\n\n\n

<\/span>Conclusions and perspectives<\/h2>\n\n\n\n

Our experimental approaches integrate genome-wide epigenetic screenings and advanced computational algorithms with the goal of better understanding the causes of cellular transformation and drug resistance. The findings of our studies will reveal novel biomarkers and regulators of resistance, thus potentially offering new targets for therapy and improving clinical outcomes, especially in subsets of patients that are challenging to treat.<\/p>\n\n\n\n

\"\"
Chromatin conformation capture (Hi-C) interaction map of a patient affected by T-ALL, showing inter-chromosomal interactivity at chromosomes 5 and 14, providing evidence of a balanced t(5;14) translocation (A) establishing a new contact between a lncRNA and the proto-oncogene TLX3 (B). The bottom panels show single-cell RNA-sequencing UMAP plots highlighting the prevalence of TLX3 signature genes for this patient (C-D).<\/em><\/figcaption><\/figure>\n\n\n\n

<\/span>Publications<\/h2>\n\n\n\n

At this link<\/a><\/strong>, you can find all the scientific publications of the Principal Investigator.<\/p>\n\n\n\t

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Selected publications<\/h2>\n\t\t\t\t
\n\t\t\t\t\t\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t\t\t\t\t\t3D chromatin hubs are regulatory units of identity and survival in human acute leukemia<\/a>\n\t\t\t\t\t\t\t\t\t\t\t\t

Gambi G*, Boccalatte F*@, Rodriguez-Hernaez J*, Lin Z, Nadorp B, Polyzos A, Tan J, Avrampou K, Inghirami G, Kentsis A, Apostolou E, Aifantis I, Tsirigos A@<\/p>\n\t\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t\t

\n\t\t\t\t\t\t\t\t\t\t\t\t\tNative stem cell transcriptional circuits define cardinal features of high-risk leukemia<\/a>\n\t\t\t\t\t\t\t\t\t\t\t\t

Wang Q*, Boccalatte F*, Xu J, Gambi G, Nadorp B, Akter F, Mullin C, Melnick AF, Choe E, McCarter AC, Jerome NA, Chen S, Lin K, Khan S, Kodgule R, Sussman JH, P\u00f6l\u00f6nen P, Rodriguez-Hernaez J, Narang S, Avrampou K, King B, Tsirigos A, Ryan RJH, Mullighan CG, Teachey DT, Tan K, Aifantis I, Chiang MY.<\/p>\n\t\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t\t

\n\t\t\t\t\t\t\t\t\t\t\t\t\tRadium 223 induces transient functional bone marrow toxicity<\/a>\n\t\t\t\t\t\t\t\t\t\t\t\t

Parlani M*, Boccalatte F* @ , Yeaton A, Wang F, Zhang J, Aifantis I, Dondossola E# @<\/p>\n\t\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t\t

\n\t\t\t\t\t\t\t\t\t\t\t\t\tThe ubiquitin ligase Huwe1 regulates the maintenance and lymphoid commitment of hematopoietic stem cells<\/a>\n\t\t\t\t\t\t\t\t\t\t\t\t

King B*, Boccalatte F*, Moran-Crusio K, Wolf E, Wang J, Kayembe C, Lazaris C, Yu X, Aranda-Orgilles B, Lasorella A and Aifantis I.<\/p>\n\t\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t\t

\n\t\t\t\t\t\t\t\t\t\t\t\t\tmiR-126 orcherstrates an oncogenic program in B-cell precursor acute lymphoblastic leukemia<\/a>\n\t\t\t\t\t\t\t\t\t\t\t\t

Nucera S*, Giustacchini A*, Boccalatte F*, Calabria A, Fanciullo C, Plati T, Ranghetti A, Garcia-Manteiga JM, Cittaro D, Benedicenti F, Lechman ER, Dick JE, Ponzoni M, Ciceri F, Montini E, Gentner B and Naldini L.<\/p>\n\t\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t\t<\/div>\n\t<\/div>\n<\/div>\n\n\t<\/div>\n","protected":false},"featured_media":1121,"template":"","meta":{"_acf_changed":true,"footnotes":""},"class_list":["post-2301","laboratory","type-laboratory","status-publish","has-post-thumbnail","hentry"],"acf":[],"yoast_head":"\nGENOMIC ARCHITECTURE OF CANCER - Istituto di Candiolo<\/title>\n<meta name=\"description\" content=\"Research topic Chromatin structure and epigenetic mechanisms for cancer growth and resistance to therapy. 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