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inv(12)(p13q15) ETV6/PTPRR

Written2013-02Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

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ICD-Morpho 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS
ICD-Morpho 9989/3 Myelodysplastic syndrome, unclassifiable
Atlas_Id 1631

Clinics and Pathology

Disease Myelodysplastic syndrome (MDS), and acute myeloid leukemias (AML)
Clinics A 75-year-old female patient presented with refractory anemia (RA) (Welborn et al., 2004). A 24-year-old female patient presneted with acute myelogenous leukemia (M2-AML) (Nakamura et al., 2005).
Prognosis The patient with RA was alive 14 months after diagnosis without treatment. The patient with M2-AML underwent bone marrow transplantation and remained in remission 44 months after diagnosis.


Another case of inv(12)(p13q15) was that of a 59 -year-old female patient with AML M2. However, the 5' part of ETV6 was translocated to chromosome15 and the 3' part of ETV6 to 12q15 (Setoyama et al., 1998). Therefore the genetic rearrangement is different.
Only the case studied by Nakamura et al., 2005 ascertained the breakpoints within ETV6 and PTPRR.


Additional anomalies +8 and additional abnormalities were present in the RA case; the inv(12) was the sole anomaly in the M2-AML case.

Genes involved and Proteins

Gene NameETV6 (ets variant 6)
Location 12p13.2
Protein 452 amino acids. ETV6 is composed of a HLH domain responsible for hetero- and homodimerization in N-term, and an ETS domain responsible for sequence specific DNA-binding in C-term (binds to the DNA sequence 5'-CCGGAAGT-3'). Transcriptional regulator; tumor suppressor. Involved in bone marrow hematopoiesis.
Gene NamePTPRR (protein tyrosine phosphatase, receptor type, R)
Location 12q15
Protein 657 amino acids. PTPRR belong to the protein tyrosine phosphatase (PTP) family. PTPRR is composed of a signal peptide, a hydrophobic region, a transmembrane region, a kinase interacting motif, and a protein tyrosine phosphatase domain. PTPRR isoforms are regulators of MAPK phosphorylation levels. Activated PKA prevents the PTPRR-MAPK binding and MAPK inhibition by phosphorylation of the KIM domain of PTPRR. PTPRR-deficient mice exhibit ataxic symptoms (Hendriks et al., 2009). PTPRR is down regulated in colorectal cancer (Menigatti et al., 2009).

Result of the chromosomal anomaly

Hybrid gene
Description The chimeric DNA joined ETV6 exons 1 to 4 and PTPRR exons 7 to 14.
Alternative splicing leads to generation of 10 ETV6/PTPRR chimeric cDNAs, of which a truncated ETV6, due to frameshift, and an ETV6/PTPRR in-frame isoform with an open reading frame of 1158 nucleotides coding for 385 amino acids, including the helix-loop-helix domain of ETV6 and most of the protein tyrosine phosphatase domain of PTPRR.
Fusion Protein
Description The ETV6/PTPRR fusion protein is made of 385 amino acids (aa), including the helix-loop-helix domain of ETV6 and most of the protein tyrosine phosphatase domain of PTPRR. 154 aa come from ETV6 and 231 from PTPRR.
Oncogenesis Both truncated ETV6 and ETV6/PTPRR were shown to affect nuclear localization of wild-type ETV6. Both can heterodimerize with wild-type ETV6. ETV6/PTPRR lacks protein tyrosine phosphatase activity. Both truncated ETV6 and ETV6/PTRPP could be important in leukemogenesis.

To be noted

Additional cases are needed to delineate the epidemiology of this rare entity:
you are welcome to submit a paper to our new Case Report section.


PTPRR protein tyrosine phosphatase isoforms and locomotion of vesicles and mice.
Hendriks WJ, Dilaver G, Noordman YE, Kremer B, Fransen JA.
Cerebellum. 2009 Jun;8(2):80-8. doi: 10.1007/s12311-008-0088-y. Epub 2009 Jan 10. (REVIEW)
PMID 19137382
The protein tyrosine phosphatase receptor type R gene is an early and frequent target of silencing in human colorectal tumorigenesis.
Menigatti M, Cattaneo E, Sabates-Bellver J, Ilinsky VV, Went P, Buffoli F, Marquez VE, Jiricny J, Marra G.
Mol Cancer. 2009 Dec 16;8:124. doi: 10.1186/1476-4598-8-124.
PMID 20015382
Cloning and characterization of the novel chimeric gene TEL/PTPRR in acute myelogenous leukemia with inv(12)(p13q13).
Nakamura F, Nakamura Y, Maki K, Sato Y, Mitani K.
Cancer Res. 2005 Aug 1;65(15):6612-21.
PMID 16061641
A unique translocation of the TEL gene in a case of acute myelogenous leukemia with inv(12)(p13q15).
Setoyama M, Tojo A, Nagamura F, Asano S, Ishimae M, Eguchi M, Kamada N.
Blood. 1998 Aug 15;92(4):1454-5.
PMID 9694736
Inversion of chromosome 12 and lineage promiscuity in hematologic malignancies.
Welborn J, Jenks H, Taplett J, Walling P.
Cancer Genet Cytogenet. 2004 Jan 15;148(2):91-103.
PMID 14734219


This paper should be referenced as such :
Huret, JL
inv(12)(p13q15) ETV6/PTPRR
Atlas Genet Cytogenet Oncol Haematol. 2013;17(7):494-495.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Other genes implicated (Data extracted from papers in the Atlas) [ 2 ]


Translocations implicated (Data extracted from papers in the Atlas)

 inv(12)(p13q15) ETV6/PTPRR

External links

ETV6 (12p13.2) PTPRR (12q15)

Mitelman databaseinv(12)(p13q15)
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9861/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9989/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
Mitelman databaseETV6/PTPRR [MCList]  ETV6 (12p13.2) PTPRR (12q15)
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed

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