Epigenetic Silencing of Is an Early Event in Cancer and Is Associated with Luminal, Receptor Positive Breast Tumor Subtypes.

Immortality is an essential characteristic of cancer cells; a recent transcriptomic study of epithelial cell immortalization has linked epigenetic silencing of the long noncoding RNA to this process. This study evaluated the epigenetic and transcriptional state of in two premalignant conditions-ductal carcinomas and colon adenomas. Results show that silencing is an early epigenetic event in human carcinogenesis, likely occurring near the point where premalignant cells gain immortality; this epigenetic silencing is maintained throughout malignant transformation and metastatic growth. Additional associations between MORT loss and clinical and molecular features of breast tumors showed that silencing of occurs predominantly in luminal, receptor-positive breast cancer; is associated with overexpression of and mutations of ; and is negatively correlated with mutations. Taken , silencing occurs early in breast carcinogenesis, probably during cellular immortalization, and precedes the development of invasive luminal breast cancer.