We report a 40-year-old woman diagnosed as having acute myeloid leukemia with CBFB-MYH11. Before and after stem cell transplantation in the phase of molecular remission of the marrow, CBFB-MYH11-positive cells were detected by RT-PCR analysis in skin lesions. The former was pathologically diagnosed as leukemic infiltration, while the latter was considered to be graft-versus-host disease. We can speculate that a low level of leukemic stem cells not detectable by RT-PCR analysis remained in the bone marrow, at least prior to transplantation. This case may suggest interesting biological features of inv(16)-type acute myeloid leukemia.

We describe a 36-month-old boy with acute monoblastic leukemia (AMoL M5a) and mixed-lineage leukemia (MLL)-AF9 rearrangement. At 18 months of age, he presented with swelling on the back of his hand that was considered to be an inflammatory change, but no hematological abnormalities were found. However, blasts with MLL-AF9 rearrangement were detected in biopsied tissue taken at the time and in peripheral blood samples taken 18 months later. These findings indicate that myeloid sarcoma with MLL-AF9 rearrangement may ultimately, though slowly, progress to AMoL.

Clinical applications of genomic biomarkers have been rapidly expanding, as has the development of molecular targeted therapies for various cancers. Ras activation has been regarded as a negative predictive marker for anti-epidermal growth factor receptor(EGFR)antibody therapy for colorectal cancer. Detection of mutations in KRAS codons 12 and 13 is widely used in clinical settings. Recent studies revealed that "minor" activating mutations such as those in KRAS codons 61 and 146, as well as NRAS mutations, contribute to resistance. Multiplex mutation testing that includes analysis of these mutations will be clinically available in the near future. We have conducted translational research in which novel biomarker candidates were evaluated using whole-exome sequencing-based mutation profiles of anti-EGFR antibody-treated samples from multiple centers in Japan. Development of the necessary infrastructure to ensure that genetic testing data are properly handled and utilized in clinical settings is also an important issue for the realization of cancer precision medicine. We have conducted pilot studies at the National Cancer Center in Japan.

The KRAS status in cancer tissue with submucosal or deeper invasion was investigated in patients with familial adenomatous polyposis (FAP). Fifteen cancerous lesions in 10 FAP patients were subjected to analysis for KRAS status. The clinical features of FAP were the dense type in 2 patients and the sparse type in 8 patients. Of the 15 cancerous lesions, 6 (40%) were identified as having wild-type KRAS and the remaining 9 (60%), as having mutated KRAS. Of the 9 mutated lesions, the G13D mutation was recognized in 4 patients and was the most frequent pattern. With regard to the KRAS status in patients with multiple cancerous lesions, 1 patient had 3 cancerous lesions of which 2 were of the mutated type and 1 was of the wild type and another patient had 4 cancerous lesions of which 3 were of the mutated type and 1 was of the wild type. These results suggest that the frequency of wild-type KRAS in cancer associated with FAP was approximately 40%, although it was lower than that in sporadic cancer. Moreover, we need to analyze the KRAS status in all cancerous lesions in clinical practice when chemotherapy with anti-epidermal growth factor receptor (EGFR) antibody is required for the treatment of FAP patients with unresectable advanced multiple cancers.

Microsatellite instability( MSI) in colorectal carcinoma is reportedly associated with resistance to 5-fluorouracil-based chemotherapy. Moreover, colorectal cancer patients aged ≤ 50 years could potentially have Lynch syndrome. In the present study, we examined 11 colorectal cancer patients with unresectable Stage IV disease who underwent resection of the primary tumor between January 2006 and December 2012. The relationship between the MSI status and the efficacy of first- line oxaliplatin-based chemotherapy was retrospectively examined. The MSI status included MSI-H in 1 patient, MSS-L in 2 patients, and MSS in 8 patients. The MSI-H in 1 patient was associated with familial adenomatous polyposis. Following chemotherapy, among 8 MSS patients, 3 showed stable disease (SD) and 1 showed partial response (PR). Moreover 2 MSH-L patients and 1 MSI-H patient showed progressive disease (PD) after chemotherapy. However, additional data collection is required to determine the effect of oxaliplatin-based chemotherapy for MSS-H or MSS-L colorectal patients aged ≤ 59 years.

Lynch syndrome is an inherited syndrome associated with the development of colorectal, endometrial, stomach, and other cancers; it is caused by defects in the mismatch repair genes. Such patients are at risk of developing multiple abdominal cancers after colectomy, and the presence of adhesions may render future abdominal surgeries difficult. We recommend that patients with Lynch syndrome should be considered good candidates for laparoscopic surgery. A 43-year-old Japanese man was admitted following a positive fecal occult blood test result. The patient was diagnosed with multiple colon cancers in the right colon. He had undergone endoscopic mucosal resection for a colon polyp when he was 24 years of age. Two people among his father's second-degree relatives had colorectal cancer, and he fulfilled the revised Bethesda guidelines. He underwent laparoscopic-assisted right hemicolectomy and D3 lymph node dissection. Microsatellite instability testing indicated the presence of MSI-H, and genetic testing demonstrated a pathogenic mutation of MLH-1.

Small bowel carcinoma is a rare tumor, for which a standardized chemotherapy regimen has not yet been established. Further, this tumor may belong to the group of Lynch syndrome-associated tumors, which are resistant to 5-fluorouracil (5-FU) -based chemotherapy. We investigated mismatch repair protein expression and K-ras gene mutation status in 8 patients with aggressive small bowel carcinoma and determined the chemotherapy regimen used in these patients. Immunohistochemical staining indicated normal mismatch repair protein expression in all surgical specimens. Of 8 patients, 4( 50%) had K-ras codon 12 mutations. Because small bowel carcinoma is not significantly associated with Lynch syndrome, 5-FU-based chemotherapy would be appropriate for the treatment of these patients. The prevalence of K-ras codon 12 mutations was relatively similar to that in patients with sporadic colorectal carcinoma, and the usefulness of anti- epidermal growth factor receptor (EGFR) antibody for the treatment of small bowel carcinoma should be evaluated in the future.

EB virus (EBV) is associated with heterogeneous lymphomas. In these lymphomas EBV+ lymphoma cells are embedded in non-neoplastic bystanders: B and T cells, macrophages. Without these bystander cells, the lymphoma cells are incapable of being engrafted in immunodeficient mice. In this context, the bystanders are tumor-supportive "inflammatory niche". Recently, EBV-infected cells produce exosomes that contain EBV specifically encoded miRNAs (EBV-miRNAs). Accordingly, we hypothesized that exosomal EBV-miRNAs might redirect tumor surrounding immune cells from tumor reactive into tumor-supportive "inflammatory niche". The EBV-miRNAs in the exosome secreted from EBV positive lymphoma cells significantly influenced on monocyte/macrophage Mo/Mf in inducing CD69, IL-10, and TNF, suggesting that EBV-miRNAs might polarize Mo/Mf into tumor associated Mf (TAM). EBV-miRNAs were required to develop lymphoproliferative disease (LPD) in vivo mouse model. Moreover, when Mfs were depleted by clodronate liposome, EBV positive tumor cells disappeared. These results suggest that lymphoma-derived secretary EBV-miRNAs regulate Mo/Mf to support the lymphoma survival or development. Most importantly, exosomal EBV-miRNAs derived from the lymphoma cells were transferred to Mf in human EBV+ lymphoma samples, which showed correlation with prognosis.