Significant differences in methylation levels of HOXA9 were observed amongst the 52 oral SCCs with respect to genomic subtype and nodal status (p = 0.014, and p = 0.024, respectively, Wilcoxon rank sum test).
We developed a modified genomic non-Negative Matrix Factorization (gNMF) clustering algorithm to cluster CGH data of tumor and cell lines to identify genomic subtypes of tumors and select representative cell lines.
Moreover, 8p12-amplified tumors were confined mainly to two genomic subtypes, the amplifier and luminal-complex subtypes, with high-level 8p12 amplification occurring primarily in the amplifier subtype.
However, luminal A-classified tumors were distributed in two main genomic subtypes, luminal-simple and luminal-complex, the former group having a better prognosis, whereas the latter group included also luminal B and the majority of BRCA2-mutated tumors.
We applied the algorithm to three major tumor types: non-small cell lung carcinoma (NSCLC), colorectal carcinoma (CRC), and malignant melanoma, identified distinct genomic subtypes for each cancer, and identified cell lines representative of each subtype.
So, while it is well-established that there are 2 genomic subtypes (RB1 −/− and RB1+/+ MYCN A) there is controversy surrounding gene expression subtypes, in particular within the RB1 −/− tumor subtype.
BRCA2 tumors clustered among luminal-complex tumors characterized mostly as luminal B, ER-positive, and histologic grade 2. The genomic subtypes were significantly associated with clinical outcome, and the observation that luminal-simple cases display a better disease outcome within the intrinsic luminal A subtype was validated in independent data sets.
This revealed six genomic subtypes with different clinical behavior and a striking concordance to the intrinsic subtypes.
Hierarchical clustering analysis of significant genomic lesions revealed genomic subtypes that displayed different clinical outcomes and high similarity to the intrinsic gene-expression subtypes previously described [ 4].
Therefore, it provides a complete characterization of genomic subtypes of the cancer under consideration and is expected to generate more precise correlates of clinical behaviour and response to drugs.
