SCIENTIFIC BACKGROUND

CBL

Category:

The CBL gene (Cas-Br-M (murine) ecotropic retroviral transforming sequence) is a proto-oncogene whose protein, E3 ubiquitin-protein ligase CBL, functions as a negative regulator of several signal transduction pathways including the Ras/MAP kinase signal transduction pathway. Somatic variants and translocations of this gene are found in many cancer types, including acute myeloid leukemia. The CBL gene is located on chromosome 11q23.

 

Juvenile myelomonocytic leukemia (JMML) is a rare form of leukemia in infancy and early childhood which is characterized by malignant transformation in the hematopoietic stem cell compartment. JMML accounts for 30% of myelodysplastic syndrome cases and 2% of all leukemias. 10 to 15% of children affected by neurofibromatosis type 1 with associated pathogenic variants in the neurofibromin gene develop JMML. Patients with Noonan syndrome or Noonan syndrome-like disorder due to germline alterations in the PTPN11, KRAS, and NRAS genes also have a predisposition to JMML. Isolated forms of JMML may include somatic PTPN11 variants as well as homozygous CBL variants.

 

In a few patients presenting with symptoms of Noonan syndrome, in whom pathogenic variants in genes typical for Noonan syndrome have been excluded, germline variants in the CBL gene can be detected. Most of these occur de novo. These patients may have concurrent JMML. This has been shown to be caused by a subsequent somatic LOH (loss of heterozygosity) on chromosome 11q23, where the CBL gene is located.

 

References

Zenker et Kutsche 2016, medgen 28:15 / Bulow et al. 2015 Am J Med Genet 167A:394 / Martinelli et al. 2010, Am J Hum Genet 87:250 / Perez et al. 2010, J Med Genet 47:686 / Niemeyer et al. 2010, Nature Genet 42:794 / De Filippi et al. 2009, Brit J Haematol 147:706 / Schubbert et al. 2006, Nature Genet 38:331 / Jongmans et al. 2005, Am J Med Genet 134A:165

GENES

CBL

ASSOCIATED TESTS

How to order

LATEST ARTICLES

Aiming to evaluate the role of chromosomal aneuploidy in pregnancy loss, a 2023 study 35 years in the making evaluated the genomic landscape of first...

Read more

Cancer is a complex genetic disease that affects millions of people in the world. It is one of the leading causes of death worldwide, with about ten ...

Read more

Researchers created a detailed map of the placenta during labor. By studying how maternal and fetal cells communicate, they discovered signals in the...

Read more

A recent paper published in Nature Medicine (1) aimed to identify genes and genomic biomarkers which can better predict outcomes and personalized the...

Read more

In honor of the international day of women and girls in science, we interviewed one of our very own, Dr. Evelina Papaioannou. Dr. Evelina Pa...

Read more

Aneuploidies, such as translocations, whole or segmental chromosomal duplications, and deletions, are examples of chromosomal abnormalities that are ...

Read more

Here you can read the winning essays from the first, annual DNA essay competition on the subject of "How unfolding the DNA code can help with precisi...

Read more

Introduction Our voices are as unique as our fingerprints! Although there are people whose voices might sound alike, there are no two voices exact...

Read more

Not everyone likes winter. For people who do not enjoy the cold weather, or having to put on a thick coat to go outside, a winter can be a source of ...

Read more

The month of November, also known as Movember, has been chosen as the month to raise awareness about men’s health. During Movember, men are encoura...

Read more