X chromosomal abnormalities in basal-like human breast cancer

Abstract

Sporadic basal-like cancers (BLC) are a distinct class of human breast cancers that are phenotypically similar to BRCA1-associated cancers. Like BRCA1-deficient tumors, most BLC lack markers of a normal inactive X chromosome (Xi). Duplication of the active X chromosome and loss of Xi characterized almost half of BLC cases tested. Others contained biparental but nonheterochromatinized X chromosomes or gains of X chromosomal DNA. These abnormalities did not lead to a global increase in X chromosome transcription but were associated with overexpression of a small subset of X chromosomal genes. Other, equally aneuploid, but non-BLC rarely displayed these X chromosome abnormalities. These results suggest that X chromosome abnormalities contribute to the pathogenesis of BLC, both inherited and sporadic.

MMSET is overexpressed in cancers: Link with tumor aggressiveness

“…Overexpression of MMSET was found in glioblastoma compared to normal brain (P = 1.7E-14, P = .009, P = .002) [11; 12; 13]; in hepatocellular carcinoma compared to normal liver (P = 2.9E-7, 1.3E-6) [14; 15]; in head and neck cancer compared to the normal (P = .008, P = 2.7E-5) [16; 17]; in bladder carcinoma compared to normal bladder (P = 4.1E-11, P = 1.8E-7) [18; 19]; in primary colon cancer compared to normal adjacent mucosa (P = 9.5E-6) [20]; in esophagus adenocarcinoma compared to normal esophagus (P = .004) [21]; in breast carcinoma compared to normal breast (P = 3.8E-8) [22]; in T-cell acute lymphoblastic leukemia compared to normal bone marrow (P = 5.1E-7) [23]; in B-cell acute lymphoblastic leukaemia compared to normal bone marrow (P = .001) [23]; in lung adenocarcinoma compared to normal lung (P = .009, P = 8.4E-4, 1.7E-6) [24; 25; 26]; in lymphoma compared to normal B-cell (P = 3.5E-5, 7.3E-5) [27]; in cutaneous melanoma compared to normal melanocyte ( P = 6.46E-13, P = .01, P =.009) [28; 29; 30]; in smoldering multiple myeloma compared to normal bone marrow (P = 7.3E-4) [31]; in prostate cancer compared to normal prostate (P = 1.8E-6, P = .039, P = 5.1E-8, P = .002, P = .009, P = .006, P = .009) [32; 33; 34; 35; 36; 37; 38]; in yolk sac tumor compared to normal testis (P = .003) [39]; in ovarian carcinoma compared to normal ovary (P = .002, P = 1.1E-4) [40; 41] and in clear cell carcinoma compared to normal kidney tissue (P = .006) [42].…”

Data driven derivation of cutoffs from a pool of 3,030 Affymetrix arrays to stratify distinct clinical types of breast cancer

“…We included 238 of our own samples (datasets Frankfurt, Frankfurt-2, and Frankfurt-3) which have been described previously (Ahr et al 2002 [9], [10], Rody et al 2008 [11], Ruckhäberle et al 2008 [12], and Rody et al 2007 [13], respectively) as well as 2792 samples from 22 different publicly available datasets (Table 1): Rotterdam [14][15][16], Mainz [17], Trans-BIG [18], Oxford-Untreated [19], London [20], London-2 [21], Oxford-Tamoxifen, Veridex-Tam [22], Stockholm [23], Uppsala [24,25], San Francisco [26], New York [27], MDA133 [28], EORTC [29], Edinburgh [30], ExpO [31], Signapore [32], Genentech [33], Boston [34], Berlin [35], Paris [36], and Tampa [37]. For comparability, only the ProbeSets from the Affymetrix HG-U133A microarray were used from seven datasets where HG-U133?…”

Role of Nek2 on centrosome duplication and aneuploidy in breast cancer cells

“…Of particular interest is Nek2, which localizes to the centrosome/centriole and 6 helps to establish a bipolar spindle by initiating the separation of centrosomes (16-18). High levels of NEK2 protein have been previously described in breast cancers (19), and Nek2 mRNA overexpression has been reported in different breast cancer subtypes (20,21). These observations, coupled with Nek2's function as a major centrosome regulator, marks this kinase as an emerging target of drug discovery interest (43)(44)(45).…”