This first study of ASXL1 mutations in primary CN-AML demonstrates that ASXL1-mutated older patients, particularly within the ELN Favorable group, have unfavorable outcomes and may be candidates for experimental treatment approaches.
Mutations in primary cilium-related genes have been linked to a number of rare developmental disorders as well as dysregulation of cell proliferation.
All these mutations in primary fibroblasts or derived iPSCs were verified by DNA sequencing.
For example, Gerlinger et al. found that over half the mutations in primary tumor and its various metastases of the same advanced renal cell carcinoma are different [166].
CONCLUSIONS: p53 immunostaining guided LCM combined with DNA-based analyses emphasizes the presence of focal p53 mutations in primary prostate cancers and underscores the significance of previous observations showing a correlation between focal p53 immunostaining in primary CaP and cancer recurrence after radical prostatectomy.
By sequencing the exons of the three hiPSC-ASPM cell clones, we identified a heterozygous mutation at 9,910 C→T ln exon 25 that introduced a premature stop codon and a homozygous mutation at 7,684 A→G in exon 18 that produced a S2562G missense mutation, which is consistent with previously reported Aspm mutations in primary microcephaly patients (Bond et al., 2003) (Fig. S3B).
Sequencing for murine HD and PEST mutations in primary mouse tumors samples was performed as described [51].
Our results demonstrate a higher percentage of KRAS mutations in primary tumors of patients with lung metastases as compared with those with liver metastases (59% vs 32%).
According to these authors, chemotherapy with DNA-damaging agents could cause mtDNA mutations in primary leukemia cells, which often exist in heteroplasmic condition.
The study identified the timing of different types of in vivo Gag mutations in primary HIV-1 subtype C infection in relation to the estimated time of seroconversion.
In addition, there was a tendency towards a higher proportion of KRAS mutations in primary tumors of patients with lung metastases than in those with liver metastases, although it did not reach statistical significance (56% vs 38%; P = 0.1027).
