Hallmark Apoptosis - BCL2 missing

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Giulia Gentile

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Mar 27, 2025, 7:39:32 AM3/27/25
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Dear all,

In Liberzon 2015, BCL2 (apoptosis regulator) is described as positively associated with proliferation (E2F hallmark) and negatively associated with the Apoptosis hallmark. However, BCL2 is not present in the previously mentioned gene sets. I am particularly interested in the Apoptosis hallmark gene set and don't understand why BCL2 family genes and BCL2-like genes are contained in the list, made up of 161 genes, except BCL2 (either in human or mouse). 
Instead, BCL2 is present in Estrogen response (early and late), Hypoxia, and IL2-STAT5 signaling hallmark gene sets and in C2 curated Apoptotic signaling and pathway gene lists from different sources.

Thank you in advance for your help.

Regards,

Giulia Gentile

Anthony Castanza

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Mar 28, 2025, 4:20:43 PM3/28/25
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Hi Giulia,

Generally, the Hallmark collection gene sets represent the genes that were most transcriptionally responsive to perturbations of the annotated process. They are not a comprehensive list of all genes involved, simply those that, in the data that was used to construct the set, represented the best markers.

Unfortunately, due to the nature of the computational approach that was used in the construction and refinement of the Hallmark gene sets (as described in the associated publication, linked on the collection information page), I can't really comment on the inclusion or exclusion of specific genes.

Sorry I couldn't be of more help here

-Anthony

Anthony S. Castanza, PhD
Curator, Molecular Signatures Database
Mesirov Lab, Department of Medicine
University of California, San Diego

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Giulia Gentile

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Mar 31, 2025, 5:16:58 AM3/31/25
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Hi Antony,

thank you very much for your answer.

I referred to the same hallmark-associated publication (PubMed 26771021, Liberzon 2015). The authors validated the hallmarks gene sets and Bcl-2 was among the validated targets. 

Thank you for your time.

Giulia Gentile
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