Editing Barr body (section)

== Role in cancer ==
The X chromosome encodes several [[Tumor suppressor gene|tumour suppressor genes]] and [[Oncogene|oncogenes]], thus incorrect dosage compensation may contribute to cancer development through their reactivation or silencing.<ref name=":13">{{Cite journal |last1=Giaimo |first1=Benedetto |last2=Robert-Finestra |first2=Teresa |last3=Oswald |first3=Franz |last4=Gribnau |first4=Joost |last5=Borggrefe |first5=Tilman |date=2021-04-01 |title=Chromatin Regulator SPEN/SHARP in X Inactivation and Disease |journal=Cancers |language=en |volume=13 |issue=7 |pages=1665 |doi=10.3390/cancers13071665 |doi-access=free |issn=2072-6694 |pmc=8036811 |pmid=33916248}}</ref> This could be achieved through poor epigenetic regulation of the Xi – it has been observed in several cancer types (medulloblastoma, glioblastoma, breast cancer, and acute myeloid leukemia) that the Xi accumulates more mutations than the autosomes.<ref name=":13" /> 

[[X-chromosome reactivation|Reactivation]] of a Barr body is possible, and has been observed in breast and ovarian cancer cells.<ref name=":0">{{Cite journal|last1=Natekar|first1=Prashant E.|last2=DeSouza|first2=Fatima M.|date=2008|title=Reactivation of inactive X chromosome in buccal smear of carcinoma of breast|journal=Indian Journal of Human Genetics|volume=14|issue=1|pages=7–8|doi=10.4103/0971-6866.42320|issn=0971-6866|pmc=2840782|pmid=20300284 |doi-access=free }}</ref> One study showed that the frequency of Barr bodies in breast carcinoma was significantly lower than in healthy controls, indicating reactivation of previously inactivated X chromosomes.<ref name=":0" /> In breast cancer cell lines, a loss of the repressive histone mark [[H3K27me3]] was observed on the inactive X chromosome, disrupting its silenced state and leading to the expression of genes that are typically repressed.<ref name=":2">{{Cite journal |last1=Chaligné |first1=Ronan |last2=Popova |first2=Tatiana |last3=Mendoza-Parra |first3=Marco-Antonio |last4=Saleem |first4=Mohamed-Ashick M. |last5=Gentien |first5=David |last6=Ban |first6=Kristen |last7=Piolot |first7=Tristan |last8=Leroy |first8=Olivier |last9=Mariani |first9=Odette |last10=Gronemeyer |first10=Hinrich |last11=Vincent-Salomon |first11=Anne |last12=Stern |first12=Marc-Henri |last13=Heard |first13=Edith |date=April 2015 |title=The inactive X chromosome is epigenetically unstable and transcriptionally labile in breast cancer |journal=Genome Research |volume=25 |issue=4 |pages=488–503 |doi=10.1101/gr.185926.114 |issn=1549-5469 |pmc=4381521 |pmid=25653311}}</ref> This includes the bi-allelic expression of X-linked genes such as [[TBL1X]] and [[HDAC8]], which may alter key pathways of transcriptional regulation, contributing to cancer [[pathogenesis]]. 

It is more widely accepted that the loss of the Barr body in female cancers is the result of the duplication of the active X chromosome through mitotic error.<ref name=":11">{{Cite journal |last1=Carone |first1=Dawn M. |last2=Lawrence |first2=Jeanne B. |date=2013 |title=Heterochromatin instability in cancer: From the Barr body to satellites and the nuclear periphery |journal=Seminars in Cancer Biology |language=en |volume=23 |issue=2 |pages=99–108 |doi=10.1016/j.semcancer.2012.06.008 |pmc=3500402 |pmid=22722067}}</ref> In any case, it is likely the abnormal over-expression of these X-linked genes that may contribute to tumour progression and cancer development.<ref name=":2" /><ref name=":11" />