BackgroundCancer progression is associated with genomic instability and an accumulation of gains and losses of DNA. The growing variety of tools for measuring genomic copy numbers, including various types of array-CGH, SNP arrays and high-throughput sequencing, calls for a coherent framework offering unified and consistent handling of single- and multi-track segmentation problems. In addition, there is a demand for highly computationally efficient segmentation algorithms, due to the emergence of very high density scans of copy number.ResultsA comprehensive Bioconductor package for copy number analysis is presented. The package offers a unified framework for single sample, multi-sample and multi-track segmentation and is based on statistically sound penalized least squares principles. Conditional on the number of breakpoints, the estimates are optimal in the least squares sense. A novel and computationally highly efficient algorithm is proposed that utilizes vector-based operations in R. Three case studies are presented.ConclusionsThe R package is a software suite for segmentation of single- and multi-track copy number data using algorithms based on coherent least squares principles.

SummaryWe present a prospective phase II study of patients with relapse after chemotherapy showing transformation of follicular lymphoma to diffuse large B‐cell lymphoma, performed before rituximab was included in standard treatment. Patients in complete (CR) or partial remission (PR) after salvage chemotherapy were eligible for high‐dose chemotherapy with autologous stem cell support (HDT). Forty‐seven patients from five Norwegian centres were included, of whom 30 (63%) received HDT. Eighteen (60%) achieved CR, seven (23%) PR and five (10%) had progressive disease following HDT. Median follow‐up for the surviving patients was 75 months; median progression‐free (PFS) and overall survival (OS) were 26 and 47 months, respectively. Median OS for all patients was 43 months, compared to only 10 months for patients not eligible for HDT. Patients receiving CD34+ enriched/B‐cell depleted grafts had inferior PFS and a trend for inferior OS compared to patients receiving non‐purged grafts (Log Rank 0·025 and 0·151, respectively). In conclusion, two thirds of patients with transformation of follicular lymphoma were eligible for HDT. The majority of patients achieved CR and a considerable number had prolonged OS. The use of in vitro purged grafts did not result in a survival benefit compared to that of non‐purged grafts.

Our aim was to examine the genetics of clonal evolution in follicular lymphoma (FL) and to identify genetic alterations associated with disease progression. A total of 100 biopsies from 44 patients diagnosed with t(14;18)-positive FL were examined by array comparative genomic hybridization. In 20 patients the patterns of somatic hypermutations (SHMs) in the variable region of heavy chain gene were additionally analyzed. Gain of chromosome X in male samples was a marker for poor outcome (P < .01). Gains involving chromosome 2, 3q, and 5 were exclusively present in FL biopsies from cases with higher grade transformation and were among the copy number alterations (CNAs) associated with inferior survival.