Fanconi-like anemia related to a FANCM mutation.

Fanconi anemia is primarily inherited as an autosomal recessive genetic disorder with common delays in diagnosis and challenging treatments. Fanconi anemia patients have a high risk of developing solid tumors, particularly in the head and neck or anogenital regions. The diagnosis of Fanconi anemia is primarily based on the chromosomal breakage but FA gene sequencing is recommended in all patients with a positive chromosome fragility test. Here, we present a 32-year-old man with advanced tonsil squamous cell carcinoma and fatal toxicity after the first cycle of chemotherapy. No anemia was present. A recent variant mutation if the FANCM gene was detected (c1511_1515delGAGTA (pArg504AsnfsTer29)). Homozygous or double heterozygous pathogenic variants have been reported in FANCM and linked to azoospermia and primary ovarian failure without anemia. Alterations in this gene have also been associated with a genetic predisposition for solid tumors (breast and ovarian cancer) and hematological malignancies (B-cell acute lymphoblastic leukemia). Due to the hypersensitivity of these patients to DNA-damaging agents such as chemotherapy and radiotherapy, surgery is the best treatment option for malignant solid tumors. Dose reductions or alternative regimens of chemotherapy and/or radiotherapy are recommended in FA patients who develop a malignant tumor.

Circulating tumour cell analysis as an early marker for relapse in stage II and III colorectal cancer patients: a pilot study

INTRODUCTION: Recent studies have identified both the prognostic and predictive utility of determining the number of circulating tumour cells (CTC) in patients with solid cancers. MATERIAL AND METHODS: In the present pilot study we evaluated the ability of two different methods to isolate CTC in combination with two strategies to enumerate CTC from patients with stages II and III surgically treated colorectal cancer (CRC). First, we used two systems for tumour cell enrichment (differential centrifugation and immunomagnetic beads), combined with two methods to enumerate CTC (real-time PCR and fl ow cytometry), to determine the most efficient combination. These experiments were performed in a model system using serial dilutions of HT29 tumour cell lines with lymphocytes. Then, CTC analysis using the technical approach selected before was performed in 109 blood samples from 16 stage II and III CRC patients during chemotherapy treatment and follow-up. RESULTS: Immunomagnetic beads followed by flow cytometry was the most efficient combination (ED=60.53; p=0.5). Two cases out of 16 patients analysed had clinical tumour relapse. In both, we detected a significant increase of CTC five and six months, respectively, before the relapse was clinically evidenced. An increase of CTC was also observed in another case without clinical evidence of relapse. The remaining cases (13) had very few or no detectable CTC and no clinical evidence of relapse (p=0.029). CONCLUSIONS: Changes in CTC numbers during follow-up might predict tumour relapse. Further evaluation of CTC prognostic and predictive value in patients with early CRC is warranted (AU)