Oncotarget: GATA3 and APOBEC3B are prognostic markers in adrenocortical carcinoma

The cover for issue 36 of


Oncotarget


features Figure 7, ”


Knockdown of APOBEC3B is associated with a lower tumor growth in an adrenocortical carcinoma xenograft mouse model,


” by Gara, et al. which reported that the role of APOBEC3B in

adrenocortical carcinoma

and the mechanisms through which its expression is regulated in

cancer

are not fully understood.

Here, the authors report that

APOBEC3B

is overexpressed in ACC and it regulates cell proliferation by inducing S phase arrest. They show high APOBEC3B expression is associated with a higher copy number gain/loss at chromosome 4 and 8 and TP53 mutation rate in ACC.

GATA3 was identified as a positive regulator of APOBEC3B expression and directly binds the APOBEC3B promoter region.

Both GATA3 and APOBEC3B expression levels were associated with patient survival.

This Oncotarget study provides novel insights into the function and regulation of APOBEC3B expression in addition to its known mutagenic ability.

This

Oncotarget

study provides novel insights into the function and regulation of APOBEC3B expression in addition to its known mutagenic ability.

Dr. Electron Kebebew from

Stanford University

said, ”

Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy.

”

The distinct pattern of DNA base alterations has been characterized in the cancer genome using high throughput deep sequencing technologies, that reflect the underlying mutational process.

Whole-genome and exome mutation analysis of

The Cancer Genome Atlas

data on multiple cancers has revealed that this pattern is consistent with the deaminase activity of the AID/APOBEC family of enzymes, therefore, implying its significance as an endogenous mutator and a crucial contributor to somatic mutations and genomic instability.

APOBEC3B is overexpressed in

ovarian cancer

cell lines and high-grade primary ovarian cancers.

In addition, APOBEC3B expression is positively correlated with the total mutation load, as well as, elevated levels of transversion mutations.

Given there are no well-established exogenous factors associated with ACC, the

Oncotarget

authors postulated whether APOBEC3B could be an endogenous mechanism of genomic instability/mutations in ACC and investigated its function in vitro and in vivo.

The Kebebew Research Team concluded in their


Oncotarget



Research Paper

, ”

APOBEC3B overexpressed in ACC, and is associated with DNA damage, S phase arrest, higher copy number alterations and TP53 mutations in ACC. For the first time, we demonstrated that GATA3 directly regulates the expression of APOBEC3B and that both are prognostic markers in ACC.

”

###

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DOI

–

https:/

/

doi.

org/

10.

18632/

oncotarget.

27703

Full text

–

https:/

/

www.

oncotarget.

com/

article/

27703/

text/

Correspondence to

– Electron Kebebew –

[email protected]

Keywords

–


adrenocortical carcinoma

,

APOBEC3B

,

GATA3

,

prognosis

,

DNA damage

About

Oncotarget

Oncotarget

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