6q deletion is frequent but unrelated to patient prognosis in breast cancer

Patrick Lebok,Albert Von Der Assen,Volkmar Müller,Uwe Heilenkötter,Hannah Bönte,Barbara Schmalfeldt,Christina Möller-Koop,Eike Burandt,Martina Kluth,Rainer Horst Krech,Luigi Terracciano,Linn Wölber,Peter Paluchowski,Guido Sauter,Christian Wilke,Isabell Witzel,Ronald Simon

doi:10.1007/s12282-021-01301-5

Abstract

BackgroundDeletions involving the long arm of chromosome 6 have been reported to occur in breast cancer, but little is known about the clinical relevance of this alteration.MethodsWe made use of a pre-existing tissue microarray with 2197 breast cancers and employed a 6q15/centromere 6 dual-labeling probe for fluorescence in situ (FISH) analysisResultsHeterozygous 6q15 deletions were found in 202 (18%) of 1099 interpretable cancers, including 19% of 804 cancers of no special type (NST), 3% of 29 lobular cancers, 7% of 41 cribriform cancers, and 28% of 18 cancers with papillary features. Homozygous deletions were not detected. In the largest subset of NST tumors, 6q15 deletions were significantly linked to advanced tumor stage and high grade (p < 0.0001 each). 6q deletions were also associated with estrogen receptor negativity (p = 0.0182), high Ki67 proliferation index (p < 0.0001), amplifications of HER2 (p = 0.0159), CCND1 (p = 0.0069), and cMYC (p = 0.0411), as well as deletions of PTEN (p = 0.0003), 8p21 (p < 0.0001), and 9p21 (p = 0.0179). However, 6q15 deletion was unrelated to patient survival in all cancers, in NST cancers, or in subsets of cancers defined by the presence or absence of lymph-node metastases.ConclusionOur data demonstrate that 6q deletion is a frequent event in breast cancer that is statistically linked to unfavorable tumor phenotype and features of genomic instability. The absence of any prognostic impact argues against a clinical applicability of 6q15 deletion testing in breast cancer patients.

Highlights

Breast cancer is the most common malignancy detected in women [1]
These included data obtained by fluorescence in situ hybridization (FISH) for amplification of HER2 [20, 22], CCND1 [20], MDM2 [20], and cMYC [20, 22] as well as for deletions of PTEN [23], 8p21 [24], and 9p21 [25] and data obtained by IHC for estrogen receptor (ER) and progesterone receptor (PR) expression as well as Ki67-labeling index (Ki67 LI) [20, 26]
6q15 deletions were significantly linked to the subset of estrogen receptor (ER) negative breast cancers: deletion was found in 24% of ER negative but only in 17% of ER-positive breast cancers (p = 0.0182) and to the molecular subtypes of HER2-positive and basal cell type cancers (p = 0.0062). 6q15 deletion was unrelated to the presence of lymphnode metastases and progesterone receptor status

Summary

Introduction

Breast cancer is the most common malignancy detected in women [1]. Surgical removal of the cancer represents the standard of care. Especially in prostate cancer—another important hormone dependent cancer—various chromosomal deletions have been shown to have substantial prognostic relevance [9,10,11,12] One of these is deletion of 6q12q21, which is commonly found in breast cancer. Studies using classical comparative genomic hybridization in 16–34 patients [13, 14], array-based copy-number screening assays in 28 patients [15], or loss of heterozygosity (LOH) analysis 42–83 patients [14, 16,17,18] reported 6q deletions in 6–50% of breast cancers Some of these studies have described an association of 6q deletions with unfavorable tumor phenotype [14, 19]. The absence of any prognostic impact argues against a clinical applicability of 6q15 deletion testing in breast cancer patients

Methods

Results

Conclusion