Coexisting genomic aberrations associated with lymph node metastasis in breast cancer.

Coexisting genomic aberrations associated with lymph node metastasis in breast cancer. J Clin Invest. 2018 Mar 15;: Authors: Bao L, Qian Z, Lyng MB, Wang L, Yu Y, Wang T, Zhang X, Yang H, Brünner N, Wang J, Ditzel HJ Abstract Single cancer cell sequencing studies currently use randomly-selected cells, limiting correlations between genomic aberrations, morphology and spatial localization. We laser-captured microdissected single cells from morphologically-distinct areas of primary breast cancer and corresponding lymph node metastasis and performed whole-exome or deep-target sequencing of greater than 100 such cells. Two major subclones co-existed in different areas of the primary tumor, and the lymph node metastasis originated from a minor subclone in the invasive front of the primary tumor with additional copy number changes including 8q gain, but no additional point mutations in driver genes. Lack of metastasis-specific driver events lead us to assess whether other clonal and subclonal genomic aberrations pre-existing in primary tumors contribute to lymph node metastasis. Gene mutations and copy number variations analyzed in five breast cancer tissue sample sets revealed that copy number variations in several genomic regions, including areas within chromosome 1p, 8q, 9p, 12q and 20q, harboring several metastasis-associated genes, were consistently associated with lymph node metastasis. Moreover, clonal expansion was observed in an a...
Source: Clinical Genitourinary Cancer - Category: Cancer & Oncology Authors: Tags: J Clin Invest Source Type: research