High Frequency of Skewed X Inactivation in Young Breast Cancer Patients

Overview

Journal J Med Genet

Specialty Genetics

Date 2002 Feb 5

PMID 11826021

Citations 28

Authors

M Kristiansen

A Langerod

G P Knudsen

B L Weber

A L Borresen-Dale

K H Orstavik

Affiliations

Soon will be listed here.

Abstract

Introduction: Patients with invasive ovarian cancer were recently shown to have a higher frequency of skewed X chromosome inactivation in peripheral blood cells compared to patients with borderline cancer and controls. In this study, we analysed the X inactivation pattern in peripheral blood from 216 breast cancer patients.

Methods: X inactivation analysis was performed using HpaII predigestion of DNA followed by PCR of the highly polymorphic CAG repeat of the androgen receptor gene (AR), which amplifies the undigested inactive X chromosome only. The X inactivation pattern was classified as skewed when 90% or more of the cells preferentially used one X chromosome.

Results: Young breast cancer patients (27-45 years) had a higher frequency of skewed X inactivation than young controls (13 and 1%, respectively) (p=0.009), whereas no difference was found for middle aged and older patients compared to controls of a similar age.

Conclusions: A germline mutation in an X linked tumour suppressor gene may give a proliferative advantage to cells with this mutation on the active X chromosome, thus causing skewed X inactivation and an increased risk for developing cancer. Another possible explanation could be that females with a constitutionally skewed X inactivation pattern are more susceptible to develop breast cancer because of an X linked low penetrance susceptibility allele that is affected by the inactivation pattern.

Citing Articles

X chromosome inactivation skewing is common in advanced carotid atherosclerotic lesions in females and predicts secondary peripheral artery events.

Buono M, Diez Benavente E, Daniels M, Mol B, Mekke J, de Borst G Biol Sex Differ. 2023; 14(1):43.

PMID: 37408072 PMC: 10324263. DOI: 10.1186/s13293-023-00527-6.

Age acquired skewed X chromosome inactivation is associated with adverse health outcomes in humans.

Roberts A, Morea A, Amar A, Zito A, El-Sayed Moustafa J, Tomlinson M Elife. 2022; 11.

PMID: 36412098 PMC: 9681199. DOI: 10.7554/eLife.78263.

BEXCIS: Bayesian methods for estimating the degree of the skewness of X chromosome inactivation.

Yu W, Zhang Y, Li M, Yang Z, Fung W, Zhao P BMC Bioinformatics. 2022; 23(1):193.

PMID: 35610583 PMC: 9128296. DOI: 10.1186/s12859-022-04721-y.

Preferential X Chromosome Inactivation as a Mechanism to Explain Female Preponderance in Myasthenia Gravis.

Nicoli V, Tabano S, Colapietro P, Maestri M, Ricciardi R, Stoccoro A Genes (Basel). 2022; 13(4).

PMID: 35456502 PMC: 9031138. DOI: 10.3390/genes13040696.

Heritability of skewed X-inactivation in female twins is tissue-specific and associated with age.

Zito A, Davies M, Tsai P, Roberts S, Andres-Ejarque R, Nardone S Nat Commun. 2019; 10(1):5339.

PMID: 31767861 PMC: 6877649. DOI: 10.1038/s41467-019-13340-w.

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