BRCA1 and BRCA2 function for the maintenance of genome stability as "Caretakers of the genome." BRCA1 is multi- functional and interacts with ATM/ATR and their substrates to regulate various cellular functions. BRCA1 is important because of its checkpoint function at S and G₂/M phages in the DNA damage response, and controls the transcription of genes such as GADD45 or RNA poly II. BRCA1 also interacts with SWI/SNF and BACH1 to regulate chromatin re-modeling. BRCA2 is also multi-functional, and regulates the repair of DNA double-strand breaks in cooperation with the MRN complex and RPA. BRCA2 interacts with Rad51 to directly repair DNA damage. In addition, BRCA2 regulates cytokinesis and centrosome duplication. New treatment is developed with inhibitors of poly(ADP-ribose)polymerase(PARP)for BRCA-deficient cells. PARPs repair single-strand DNA breaks, and inhibition of PARPs is considered to break the replication fork and increase the effect of anti-cancer drugs. Inhibition of PARPs leads to the conversion of single-strand breaks(SSB)to double-strand breaks(DSB). Because BRCA1- or BRCA2-deficient cells are unable to efficiently complete homologous recombination, PARP inhibition in these cells causes a high degree of genomic instability and eventual cell death termed "synthetic lethality. "This synthetic lethal approach has been validated in studies that show striking single-agent activity of PARP inhibitors in preclinical models of BRCA1 and BRCA2 inactivation.

We report a 54-year-old man with acute myeloid leukemia (AML) carrying del(7)(q32) and inv(16)(p13q22). He was diagnosed as having AML M4Eo according to the FAB classification. RT-PCR for CBFβ/MYH11 gene was positive. Karyotype analysis revealed the primary chromosomal abnormality to be del(7)(q32) and inv(16)(p13q22) developed as a secondary abnormality. He achieved complete remission after one course of induction chemotherapy and remained in remission after several courses of consolidation therapy. del(7q) is classified into an intermediate risk group or an adverse risk group, while inv(16)/t(16;16) is classified into a favorable risk group. Some AML cases with inv(16)/t(16;16) exhibit del(7q) as an additional chromosomal abnormality. It was reported that such cases showed good prognosis despite the presence of del(7q). However, AML cases with del(7q) and inv(16)/t(16;16) as secondary chromosomal abnormalities are rare. Further study is needed to clarify the clinical manifestations of such cases.

A man in his fifties had a medical checkup. Mucosal papillomatosis in his oral cavity and palmoplantar keratosis were observed. Esophagogastroduodenoscopy revealed multiple polypoid lesions both in the esophagus and stomach. In addition, colonoscopy showed schwannoma in the rectum. He underwent an operation for adenomatous goiter. At first his typical esophageal multiple polypoid lesion was a diagnostic cue to Cowden disease (CD). Other clinical findings convinced us that he was suffering from CD. He was, then, diagnosed as CD according to the criteria of International Cowden Consortium although he had no family medical history suspicious of CD. Interestingly, genetic testing revealed that the patient had a germline mutation in exon5 of PTEN on chromosome 10. It was a point mutation of C to T transition at codon130, resulting in nonsense mutation (CGA→TGA). A close follow-up, especially cancer surveillance, is necessary for him since CD is associated with a high risk of developing malignant disease. It is noted that the typical esophageal features can be a diagnostic cue to CD, as shown in the present case.

A 61-year-old female was diagnosed with multiple myeloma (MM) in 2001. After treatment with chemotherapy containing alkylating agents and thalidomide, she underwent autologous stem cell transplantation in 2003, with high-dose melphalan as a conditioning regimen. Thalidomide was also given after the transplant from July 2003 to November 2005 for residual disease and she remained in partial remission. In October 2008, she developed pancytopenia. Bone marrow examination confirmed the diagnosis of acute B lymphoblastic leukemia (B-ALL). We performed IgH gene rearrangement studies on genomic DNA which revealed the MM, and ALL seemed to be derived from different clones. The development of MM and ALL in the same patient is a very rare event. Further accumulation of the cases to understand the mechanism underlying this event is warranted.

We present a case with sustained complete molecular response (CMR) after cessation of two months of imatinib mesylate (IM) treatment for chronic myelogenous leukemia (CML) relapsed after allogeneic stem cell transplantation (Allo-SCT). A 30-year-old previously healthy woman was seen in a clinic because of left abdominal discomfort. Splenomegaly and increased leukocytes with Philadelphia chromosome led to the diagnosis of CML in the accelerated phase. She received four months of IM treatment followed by allo-SCT from her HLA-matched sibling. She achieved and maintained CMR without developing acute GVHD for six months, when hematologic relapse occurred. While reducing the immunosuppressant, she received IM; however, it was discontinued two months later due to myelosuppression. Even after the termination of IM, the positivity of chimeric BCR-ABL gene detected by FISH analysis in peripheral blood continued to decrease. The molecular analysis of bone marrow one year after allo-PBSCT revealed CMR lasting for more than two years after cessation of IM. IM may possibly enhance the graft-versus-leukemia effects by reducing tumor burden in cases relapsed after allo-SCT.

A previous large, randomized, control trial(JBR.10)revealed that adjuvant chemotherapy with cisplatin(CDDP) and vinorelbine(VNR)was effective for non-small-cell lung cancer(NSCLC). It was also reported that adjuvant chemotherapy was not effective for p53-negative or K-ras mutation-positive patients. To clarify whether p53 and ras statuses are true predictive markers for chemotherapy with cisplatin, chemosensitivity was examined using an in vitro drug sensitivity assay.

We report an extremely rare case of a 69-year-old man having a retroperitoneal carcinoid tumor associated with multiple endocrine neoplasia (MEN) type 1. The patient whose son and daughter were previously diagnosed with MEN type 1 was admitted to the Department of Endocrinology at our hospital for evaluation of this disorder. Computed tomography (CT) and ultrasonography revealed a parathyroid and retroperitoneal tumor (43 mm x 34 mm). The patient did not consent to surgical management of the tumor; however three years later, a follow-up CT revealed tumor enlargement (55 mm x 50 mm). We were unable to rule out a malignancy, and subsequently resected the tumor. A pathological diagnosis of retroperitoneal carcinoid was made. No local recurrence or metastasis have been observed for 21 months.

A 35-year-old man admitted to the hospital for oral hemorrhage was diagnosed with acute promyelocytic leukemia (APL). Remission from APL was achieved by induction therapy with all-trans retinoic acid (ATRA); the PML/RARA fusion gene was not detected on PCR analysis. Despite complete molecular remission, severe persistent pancytopenia, massive ascites, and renal failure were observed. The liver surface appeared rough and irregular on computed tomographic images. On the basis of the liver biopsy results, we diagnosed his condition as portal hypertension due to autoimmune hepatitis. Indocyanine green test showed good residual function of the liver, and therefore, 2 courses of consolidation therapy were administered; chemotherapy was stopped because of severe pancytopenia due to portal hypertension. Instead of continuing the consolidation therapy, maintenance therapy involving 8 rounds of ATRA monotherapy (45 mg/m(2), days1∼14) was initiated. Portal hypertension did not progress further with this maintenance therapy and therefore it was continued. The patient has been in remission from APL ever since, and no relapses have occurred since the past 5 years. These results suggest that ATRA can be used for long-term therapy in such cases.