Only four cases in the whole study had both a mutation and gain of copy number of PIK3CA.
To determine the relation between somatic mutation and gain of gene copy number of PIK3CA gene in breast cancer, we integrated our mutation and gene copy number data.
We did not observe a significant association between somatic mutation and gain of PIK3CA gene copy number in 92 cases of breast tumors (Table 2).
In regard to RFS, patients with wild-type HER2 mRNA < 400 (P=0.066), mutation and gain of PIK3CA (P=0.06), gain of CDH3 (P<0.001), BIRC5 (P=0.007), MYBL2 (P=0.013), or AIB1 (P=0.013) had or tended to have worse RFS rates than those without.
Integration of the CNA and mutation status that were specific to EFS24 failures revealed that 77% of patients who fail to achieve EFS24 have a combination of four variants (FOXO1 mutation and gains in 3q27.3, 11q23.3 and 19q13.32; Figure 3b).
Here we found that the CHEK2 locus was lost in fewer than one third of our mutation-carrier samples and gained in some, with the majority not showing evidence for copy-number variation.
By comparing deep sequencing results of a basal-like TN patient breast tumor, blood, metastasis and PDX, Ding and colleagues [ 7] found that the PDX retained the mutations of the primary tumor and gained additional mutations comparable to the patient metastasis.
We suggest that this example of how a protein-coding gene loses its protein-coding function by mutation and then gains a new function due to transposon integration is not an exceptional case, but is a more wide-spread phenomenon applying to other non-coding RNA genes and pseudogenes with new functions.
This view is strengthened by the association of cluster B2 with scar-like tumor fibrosis, a desmoplastic reaction which is common in localized peripheral lung adenocarcinoma, and of cluster B3 with the highest rate of EGFR mutation (93%) as well as the highest rate of the co-occurrence of EFGR mutations and gains or amplifications on 7p (86%).
Although this phenotype has been described in Brugada syndrome due to Na+ channel mutations and gain-of-function Kv11.1 mutant channels [39], it has not been previously reported with dominant-negative Kv11.1 mutations associated with LQT2.
