Wednesday, November 23, 2011

del 13 q14: size matters

In Leukemia Research on line

Chronic lymphocytic leukemia (CLL) is a highly heterogeneous disease which has proven amenable to subtyping through genomic microarray analysis. Initially, 13q14 deletions as an isolated finding were associated with a favorable prognosis. However, recent evidence has revealed significant heterogeneity within the 13q14 deletion subtype, thus, there is a clear clinical need for more precise stratification of 13q14 deletions at the genomic level. The minimal deleted region (MDR) includes: DLEU2, DLEU7, MIR15A/MIR16-1 and part of DLEU1. Recent studies suggest that in addition to the MDR, the size of the deletion and the involvement of the nearby tumor suppressor gene RB1 serve as an independent prognostic biomarker for disease progression. Nine individuals in whom a 13q deletion had previously been identified by bacterial artificial chromosome (BAC) array were re-analyzed using the Cancer Cytogenomics Microarray Consortium's consensus design on an Agilent (Santa Clara, CA) 180K oligonucleotide platform. Based on the size and location of the 13q14 deletion, cases were further classified as having type (smaller, not including RB1) or type II (larger, including RB1) deletions, as described by Ouilette et al. (Cancer Res, 2008). Type I deletions were seen in 77% of cases, and Type II deletions in 22%. There was a single case of a biallelic 13q14 deletion. Deleted regions ranged in size from 1.0 to 9.8 Mb. Unlike older BAC technologies that are subject to limited resolution, the CCMC 180K oligonucleotide array allowed for further clarification of 13q deletion cases, providing valuable clinical and prognostic information for CLL.


Anonymous said...

What prognosis or Binet rating would you have if you had a Type II deletion?

jen said...

Dr.Hamblin, six years ago, I wrote to you to get some advice on my fathers CLL diagnonsis and treatment. My dad passed last week. Because of your information I was able to get my family to search for a doctor that was up to date on the latest CLL treatments. We found one(Jack Goldberg,Univ. of Penn.) and he gave us six more years with my dad. The other doctors wanted to treat him with massive amounts of chemo and had no clue about monoclonal antibodies. I wrote back then to thank you and just wanted to thank you again for your information and all your work in the CLL field. I was blessed to have come upon your work, thank you.

Terry Hamblin said...

A type II deletion does not affect Binet stage. It does adversely affect prognosis.