Atlas of Genetics and Cytogenetics in Oncology and Haematology

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

t(12;15)(p13;q25) ETV6/NTRK3 in solid tumors

Written2019-11Jean-Loup Huret

(Note : for Links provided by Atlas : click)


Abstract Review on t(12;15)(p13;q25) in solid tumors, with data on clinics, and the genes involved.


ICD-Morpho 8825/1
ICD-Morpho 8814/3
ICD-Morpho 8502/3
ICD-Morpho 8960/1
ICD-Morpho 8260/3
ICD-Morpho 9425/3
ICD-Morpho 9401/3
ICD-Morpho 8770/1
ICD-Morpho 8720/3
ICD-Morpho 8140/3
Atlas_Id 5267
Phylum Digestive organs: Colon-Rectum::
WHO/OMS Classification Digestive organs

Clinics and Pathology

Note A t(12;15)(p13;q25) ETV6/NTRK3 has been found: 1) in congenital/infantile fibrosarcoma and cellular mesoblastic nephroma (which may be a renal form of infantile fibrosarcoma), 2) in secretory breast (ductal) carcinoma and in it's analogue in the salivary glands, 3) in acute leukemias (both myeloid and lymphoid), 4) in papillary thyroid carcinoma, often radiation-associated, 5) in inflammatory myofibroblastic tumor, and, in few cases, in other tumors.
Equivalents of the ETV6/NTRK3 fusion was also found in rare instances in the above mentioned tumors: EML4 /NTRK3, MYH9 /NTRK3, MYO5A /NTRK3, LMNA / NTRK1, and ETV6/?
Disease Congenital/infantile fibrosarcoma (WHO/OMS 8814/3) (CIF)
Note Congenital/infantile fibrosarcoma is a low-grade malignant spindle cell tumor of the soft tissues that usually presents before the age of 2 years (diagnosed at birth in 40%, before 6 months in 60% of cases, more common in boys than in girls), occurring 1) most often in the extremities and with a good prognosis, at times 2) in the axial skeleton with a somewhat worse prognosis. Local recurrence is common (10 to 30 % of cases) but metastases are rare. Overall 5-year survival is at least 90% (Farmakis et al., 2014). CIF accounts for 10% of soft tissue tumors in infants.
Cytogenetics A t(12;15)(p13;q25) ETV6/NTRK3 was found in most cases, but is not found in either infantile fibromatosis, a close but benign entity, or in fibrosarcoma of the adulthood. The t(12;15) ETV6/NTRK3 is most often accompanied with trisomy or tetrasomy 11 (Knezevich et al., 1998; Rubin et al., 1998; Bourgeois et al., 2000; Punnett et al., 2000; Argani et al., 2001; Dubus et al., 2001; Sheng et al., 2001; Miura et al., 2002; McCahon et al., 2003; Ramphal et al., 2003; Morerio et al., 2004; Nonaka and Sun, 2004; Himori et al., 2005; Rizkalla et al., 2011).
The reciprocal NTRK3/ETV6 fusion product may also be found, with NTRK3 exon 14 fused to ETV6 exon 6 (Dubus et al., 2001).
A t(2;15)(p21;q24) EML4/NTRK3 has also been found in two cases of CIF. One was a 9-mo-old male patient with recurrent congenital fibrosarcoma and a history of left upper extremity hemimelia without other congenital anomalies. Exon 2 of EML4 was fused to exon 14 of NTRK3 (Tannenbaum-Dvir et al., 2015; Church et al., 2018).
A congenital infantile fibrosarcoma was found to harbor a LMNA/NTRK1 gene fusion (Wong et al., 2015).

Disease Congenital Mesoblastic Nephroma (WHO/OMS 8960/1) (CMN)
Note Congenital mesoblastic nephroma is the most common kidney tumor found in infants younger than 6 months and and accounts for 3-5% of all paediatric renal neoplasm. The 5-year event-free survival rate is 95%.
Histopathologically, it consist of spindled cells. There are three histologic subtypes: classic, mixed, and cellular. The cellular subtype is identical to infantile fibrosarcoma and is the form with a t(12;15) ETV6/NTRK3 and trisomy 11 (PDQ Pediatric Treatment Editorial Board, 2019). Cellular mesoblastic nephroma tends to present later in infanc than the classic formy, and can exhibit aggressive behavior including metastases (Bayindir et al., 2009). It has been suggested that the cellular subtype represents in fact congenital infantile fibrosarcoma occurring in the kidney (Bayindir et al., 2009; El Demellawy et al., 2016).
A t(12;15) ETV6/NTRK3, most often accompanied with trisomy or tetrasomy 11, or a fusion ETV6/NTRK3 has been found in more than 40 cases; some cases were mixed forms; none was classical form (Rubin et al., 1998; Knezevich et al., 1998; Argani et al., 2000; Ramachandran et al., 2001; Watanabe et al., 2002; Henno et al., 2003; Anderson et al., 2006; Bayindir et al., 2009).
Cytogenetics Although the t(12;15)(p13;q25) ETV6/NTRK3 was found in most cases , a t(2;15)(p21;q24) EML4/NTRK3 has also been found in one case of CMN (Church et al., 2018).

Disease Breast Ductal carcinoma - Secretory breast carcinoma subtype (WHO/OMS 8502/3) (SBC)
Note Secretory breast carcinoma is a rare (less than 0.15% of all breast cancers) subtype of breast ductal carcinoma (but the most common breast cancer in the pediatric population), with a distinct morphology: eosinophilic secretion and positive periodic acid-Schiff (PAS) secretions are seen, immune-positivity for S100 and mammaglobin, most often triple negativity (ESR1/2-, PGR-, ERBB2-)) and an excellent prognosis in children and adolescents. It occurs in both children and adults with a wide age range from 3 to 83 years. Most reported cases are in young women, with a median age of 25 years. There are only 120 cases published in literature, including 32 in male patients. Breast secretory carcinoma is a slow-growing, low-grade subtype of infiltrating ductal carcinoma. The disease seems slightly more aggressive in adults (Vasudev and Onuma 2011; Ghilli et al., 2018).
Cytogenetics A t(12;15)(p13;q25) ETV6/NTRK3 was found in most cases (Tognon et al., 2002; Diallo et al., 2003; Stransky et al 2014).
Genes ETV6/NTRK3 chimeric product can transform normal mouse mammary epithelial cells.
Fusion was between ETV6 nucleotide 1033 and NTRK3 nucleotide 1601 as previously shown for sarcoma-associated fusions (Knezevich et al., 1998). This differs from the ETV6/NTRK3 gene fusion reported in a case of acute myeloid leukemia, in which ETV6 exon 5 was not present in the fusion (Eguchi et al., 1999).
The rare secretory breast carcinomas with metastases, more aggressive tumors, showed amplification of the 16p13.3 locus, a TERT promotor mutation and loss of 9p21.3 locus (Hoda et al., 2019).

Disease Mammary analogue secretory carcinoma of salivary glands (MASC)
Note A t(12;15)(p13;q25) ETV6/NTRK3 was found in salivary gland tumors (mostly from the parotid gland) with histo-morphologic and immune-histochemical features reminiscent of secretory carcinoma of the breast, with eosinophilic secretion, positivity for PAS, S-100 protein and mammaglobin (Skálová et al., 2010; Chiosea et al., 2012; Connor et al., 2012; Skálová et al., 2014; Pinto et al., 2014). More than 250 cases have been described (review in Skálová et al., 2017). Mean age was 47 years (14-78 years), there is a slight male predominance. MASC mimick other salivary tumors, most often adenocarcinoma, not otherwise specified and acinic cell carcinomas.
MASC usually behaves indolently, but like other low-grade salivary gland carcinomas, there is some loco-regional recurrence and distant metastases (Skálová et al., 2017).
Cytogenetics A t(12;15)(p13;q25) ETV6/NTRK3 was found in most cases.
A few cases where ETV6 was fused with an unknown partner different from NTRK3 were described; these may behave more aggressively (Ito et al., 2015; Skálová et al., 2016).

Disease Thyroid: Papillary thyroid carcinoma (WHO/OMS 8260/3) (PTC)
Note In an analysis of 62 radiation-associated papillary thyroid carcinomas post-Chernobyl (iodine-131 exposure), 9 (14.5%) of PTCs harbored ETV6/NTRK3 rearrangement; ETV6/NTRK3 fusion was the second most common rearrangement type after "RET/PTC". Further screening of 151 sporadic PTCs revealed three positive cases, resulting in a prevalence of 2%. The majority of post-radiation-associated PTCs with ETV6/NTRK3 rearrangement were classified as the follicular variant of PTC (Leeman-Neill et al 2014). In a study of 496 papillary thyroid carcinoma without radiation exposure, and classified as low risk, 5 cases (three "classical", one "follicular") presented with an ETV6/NTRK3 rearrangement. Ages and sex: were: 41/F, 36/F, 23/F, 17/F) (The Cancer Genome 2014). Another genome sequencing study from "The Cancer Genome Atlas" (TCGA) found 6 such cases (Stransky et al 2014).

Disease Inflammatory myofibroblastic tumor/myofibroblastic sarcoma (WHO/OMS 8825/1) (IMT)
Note Inflammatory myofibroblastic tumor is a rare visceral and soft tissue tumor (commonly seen in the lung), consisting of myofibroblastic spindle cells with inflammatory cells. Local recurrences are seen in about 25% of patient, but metastases are rare. It affects primarily children and young adults, with a slight male predominance. Favorable outcome is documented in most cases.
An ETV6/NTRK3 fusion was found in at least 6 cases of .inflammatory myofibroblastic tumor: in a 17-year-old girl and in 2 other cases in a subset of ALK-negative inflammatory myofibroblastic tumors, in a 7-year old child and in a 23-year-old adult patient, and in a 44-year-old female patient (Alassiri et al 2016; Yamamoto et al 2016; Takahashi et al 2018).

Disease Skin melanocytic tumors (WHO/OMS 8770/1 and 8720/3) and other skin carcinomas
Note A t(12;15)(p13;q25) ETV6/NTRK3 was found in 4 cases of atypical Spitz tumors (Yeh et al., 2016), a group of cutaneous melanocytic tumors (Murali et al., 2012 Ages and sex were: 2/F, 6/F, 7/M, and 10/F (Yeh et al., 2016).
An ETV6/NTRK3 fusion was also detected in a skin melanoma in massive data sets from genome sequencing studies from the TCGA (Stransky et al 2014).
Asecretory carcinoma of the skin mimicking secretory carcinoma of the breast and the and secretory carcinoma salivary gland was found to harbor an ETV6/NTRK3 fusion gene (Huang et al., 2016)
Cytogenetics Other cases presented with the following translocations/genes fusions: MYH9/NTRK3 and MYO5A/NTRK3. In all those cases, NTRK3 fusions constitutively activated the RAS/RAF/MAPK, PI3K/AKT/MTOR and PLCG pathways in melanocytes (Yeh et al., 2016).

Disease Brain tumors (WHO/OMS 9425/3 9401/3)
Note In a series of 149 pediatric low-grade gliomas, an ETV6/NTRK3 fusion was found in a 13-year-old girl with a pilomyxoid astrocytoma (Zhang et al 2013).
An ETV6/NTRK3 fusion was also found in a high grade astrocytoma (massive data from genome sequencing) (Wu et al 2014).
Cytogenetics The reciprocal NTRK3/ETV6 fusion product was also found (Zhang et al 2013).

Disease Colon adenocarcinoma (WHO/OMS 8140/3)
Note At least 4 cases of colorectal carcinoma were found to have an ETV6/NTRK3 fusion, in massive data from genome sequencing studies from the TCGA (Seshagiri et al 2012; Stransky et al 2014; Hu et al 2018).

Disease Sinonasal adenocarcinoma
Note Two cases of low grade sinonasal adenocarcinoma were found to have the t(12;15)(p13;q25) ETV6/NTRK3 (Andreasen et al 2017).
Cytogenetics Another case presented with ETV6 fused to an unknown partner (Andreasen et al 2017).

Genes involved and Proteins

Gene NameETV6 (ets variant 6)
Location 12p13.2
Protein ETV6 is a strong transcriptional repressor. ETV6 is a 452 amino acid member of the ETS family (signal-dependent transcriptional regulators, mediating cell proliferation, differentiation and tumorigenesis). The ETV6 protein contains two major domains, the HLH (helix-loop-helix) and ETS domains. The N-term HLH domain, also referred to as the pointed or sterile alpha motif domain, is responsible for hetero- and homo-dimerization. The C-term ETS domain is responsible for sequence specific DNA-binding and protein-protein interaction. A central domain, called internal domain, is involved in the recruitment of a repression complex including NCOR1, NCOR2, and SIN3A (Braekeleer et al., 2014 ).

Gene NameNTRK3 (neurotrophic tyrosine kinase, receptor, type 3)
Location 15q25.3
Protein NTRK3 is a transmembrane receptor tyrosine kinase which triggers PI3K/AKT, RAS/RAF/MAPK, and PLCG pathways. NTRK3 is a 839 amino acid protein with a N-term extra-cellular ligand binding domain, a transmembrane domain, and a C-term intracellular tyrosine kinase domain. Ligand for NTRK3 is NTF3 (neurotrophin 3) (Knezevich 2004

Result of the chromosomal anomaly

Hybrid Gene
Description In solid tumors, ETV6 exon 5 - NTRK3 exon 15 fusion is the most frequent:
The fusion was exon 4 - exon 14 in most papillary thyroid carcinoma ceases, but one exon 5 - exon 14 fusion case was also found (Leeman-Neill et al., 2014)
The fusion was exon 5 - exon 15 in: secretory ductal breast carcinoma (Tognon et al., 2002), congenital mesoblastic nephroma (Knezevich et al., 1998; Rubin et al., 1998; Argani et al., 2000; Ramachandran et al., 2001; Watanabe et al., 2002; Henno et al., 2003; Anderson et al., 2006; Bayindir et al., 2009), secretory carcinoma of salivary glands (mammary analogue) (Skálová et al., 2010; Skálová et al., 2014), atypical Spitz tumors (Yeh et al., 2016), and also in a case of colon adenocarcinoma (Seshagiri et al., 2012). The classical exon 5 - exon 15 fusion is also found in congenital/infantile fibrosarcoma (Knezevich et al., 1998; Rubin et al., 1998; Bourgeois et al., 2000; Punnett et al., 2000; Argani et al., 2001; Dubus et al., 2001; Sheng et al., 2001; Miura et al., 2002; McCahon et al., 2003; Ramphal et al., 2003; Nonaka and Sun, 2004; Himori et al., 2005), but, also, a fusion NTRK3 exon 14 - ETV6 exon 6 was found in one case (Dubus et al., 2001).
In most leukemia cases, ETV6 exon 5 was fused to NTRK3 exon 15 (Forghieri et al., 2011; Roberts et al., 2014). In one case ETV6 exon 4 was fused to NTRK3 exon 15 (Eguchi: et al., 1999), and in another case, fusion transcripts contain ETV6 exons 1 through 5 fused to NTRK3 exons 13b and 14b or NTRK3 exons 13 through 18 (Kralik et al., 2011).
Fusion Protein
Description The SAM-PNT (sterile alpha motif- pointed) domain of ETV6 is fused to the PTK (Protein Tyrosine Kinase domain) of NTRK3.
Oncogenesis It leads to dimerization, and induction of CCND1 (cyclin D1) and increased cell cycle progression. ETV6/NTRK3 also leads to constitutive activation of the PI3K/AKT, RAS/RAF/MAPK, and PLCG pathways (Lannon and Sorensen, 2005).

To be noted

Therapeutic trials with TRK-(tropomyosin receptor kinase) inhibitors are being developed with some remarkable successes (Lange and Lo, 2018).


ETV6-NTRK3 Is Expressed in a Subset of ALK-Negative Inflammatory Myofibroblastic Tumors
Alassiri AH, Ali RH, Shen Y, Lum A, Strahlendorf C, Deyell R, Rassekh R, Sorensen PH, Laskin J, Marra M, Yip S, Lee CH, Ng TL
Am J Surg Pathol 2016 Aug;40(8):1051-61
PMID 27259007
Expression of ETV6-NTRK in classical, cellular and mixed subtypes of congenital mesoblastic nephroma
Anderson J, Gibson S, Sebire NJ
Histopathology 2006 May;48(6):748-53
PMID 16681692
ETV6 Gene Rearrangements Characterize a Morphologically Distinct Subset of Sinonasal Low-grade Non-intestinal-type Adenocarcinoma: A Novel Translocation-associated Carcinoma Restricted to the Sinonasal Tract
Andreasen S, Skálová A, Agaimy A, Bishop JA, Laco J, Leivo I, Franchi A, Larsen SR, Erentaite D, Ulhøi BP, von Buchwald C, Melchior LC, Michal M, Kiss K
Am J Surg Pathol 2017 Nov;41(11):1552-1560
PMID 28719468
Reduced sensitivity of paraffin-based RT-PCR assays for ETV6-NTRK3 fusion transcripts in morphologically defined infantile fibrosarcoma
Argani P, Fritsch MK, Shuster AE, Perlman EJ, Coffin CM
Am J Surg Pathol 2001 Nov;25(11):1461-4
PMID 11684968
Cellular mesoblastic nephroma (infantile renal fibrosarcoma): institutional review of the clinical, diagnostic imaging, and pathologic features of a distinctive neoplasm of infancy
Bayindir P, Guillerman RP, Hicks MJ, Chintagumpala MM
Pediatr Radiol 2009 Oct;39(10):1066-74
PMID 19629465
Molecular detection of the ETV6-NTRK3 gene fusion differentiates congenital fibrosarcoma from other childhood spindle cell tumors
Bourgeois JM, Knezevich SR, Mathers JA, Sorensen PH
Am J Surg Pathol 2000 Jul;24(7):937-46
PMID 10895816
Integrated genomic characterization of papillary thyroid carcinoma
Cancer Genome Atlas Research Network
Cell 2014 Oct 23;159(3):676-90
PMID 25417114
Clinicopathological characterization of mammary analogue secretory carcinoma of salivary glands
Chiosea SI, Griffith C, Assaad A, Seethala RR
Histopathology 2012 Sep;61(3):387-94
PMID 22372712
Recurrent EML4-NTRK3 fusions in infantile fibrosarcoma and congenital mesoblastic nephroma suggest a revised testing strategy
Church AJ, Calicchio ML, Nardi V, Skalova A, Pinto A, Dillon DA, Gomez-Fernandez CR, Manoj N, Haimes JD, Stahl JA, Dela Cruz FS, Tannenbaum-Dvir S, Glade-Bender JL, Kung AL, DuBois SG, Kozakewich HP, Janeway KA, Perez-Atayde AR, Harris MH
Mod Pathol 2018 Mar;31(3):463-473
PMID 29099503
Mammary analog secretory carcinoma of salivary gland origin with the ETV6 gene rearrangement by FISH: expanded morphologic and immunohistochemical spectrum of a recently described entity
Connor A, Perez-Ordoñez B, Shago M, Skálová A, Weinreb I
Am J Surg Pathol 2012 Jan;36(1):27-34
PMID 21989350
Secretory carcinoma of the breast: a genetically defined carcinoma entity
Diallo R, Tognon C, Knezevich SR, Sorensen P, Poremba C
Verh Dtsch Ges Pathol 2003;87:193-203
PMID 16888913
The detection of Tel-TrkC chimeric transcripts is more specific than TrkC immunoreactivity for the diagnosis of congenital fibrosarcoma
Dubus P, Coindre JM, Groppi A, Jouan H, Ferrer J, Cohen C, Rivel J, Copin MC, Leroy JP, de Muret A, Merlio JP
J Pathol 2001 Jan;193(1):88-94
PMID 11169520
Fusion of ETV6 to neurotrophin-3 receptor TRKC in acute myeloid leukemia with t(12;15)(p13;q25)
Eguchi M, Eguchi-Ishimae M, Tojo A, Morishita K, Suzuki K, Sato Y, Kudoh S, Tanaka K, Setoyama M, Nagamura F, Asano S, Kamada N
Blood 1999 Feb 15;93(4):1355-63
PMID 9949179
Congenital mesoblastic nephroma: a study of 19 cases using immunohistochemistry and ETV6-NTRK3 fusion gene rearrangement
El Demellawy D, Cundiff CA, Nasr A, Ozolek JA, Elawabdeh N, Caltharp SA, Masoudian P, Sullivan KJ, de Nanassy J, Shehata BM
Pathology 2016 Jan;48(1):47-50
PMID 27020209
Congenital infantile fibrosarcoma
Farmakis SG, Herman TE, Siegel MJ
J Perinatol 2014 Apr;34(4):329-30
PMID 24675019
Chronic eosinophilic leukaemia with ETV6-NTRK3 fusion transcript in an elderly patient affected with pancreatic carcinoma
Forghieri F, Morselli M, Potenza L, Maccaferri M, Pedrazzi L, Paolini A, Bonacorsi G, Artusi T, Giacobbi F, Corradini G, Barozzi P, Zucchini P, Marasca R, Narni F, Crescenzi B, Mecucci C, Falini B, Torelli G, Luppi M
Eur J Haematol 2011 Apr;86(4):352-5
PMID 21226763
Male secretory breast cancer: case in a 6-year-old boy with a peculiar gene duplication and review of the literature
Ghilli M, Mariniello MD, Scatena C, Dosa L, Traficante G, Tamburini A, Caporalini C, Buccoliero AM, Facchini F, Colizzi L, Quattrini Li A, Landucci E, Manca G, Naccarato AG, Caramella D, Favre C, Roncella M
Breast Cancer Res Treat 2018 Aug;170(3):445-454
PMID 29616377
Genomic analyses identify recurrent MEF2D fusions in acute lymphoblastic leukaemia
Gu Z, Churchman M, Roberts K, Li Y, Liu Y, Harvey RC, McCastlain K, Reshmi SC, Payne-Turner D, Iacobucci I, Shao Y, Chen IM, Valentine M, Pei D, Mungall KL, Mungall AJ, Ma Y, Moore R, Marra M, Stonerock E, Gastier-Foster JM, Devidas M, Dai Y, Wood B, Borowitz M, Larsen EE, Maloney K, Mattano LA Jr, Angiolillo A, Salzer WL, Burke MJ, Gianni F, Spinelli O, Radich JP, Minden MD, Moorman AV, Patel B, Fielding AK, Rowe JM, Luger SM, Bhatia R, Aldoss I, Forman SJ, Kohlschmidt J, Mrózek K, Marcucci G, Bloomfield CD, Stock W, Kornblau S, Kantarjian HM, Konopleva M, Paietta E, Willman CL, Loh ML, Hunger SP, Mullighan CG
Nat Commun 2016 Nov 8;7:13331
PMID 27824051
Cellular mesoblastic nephroma: morphologic, cytogenetic and molecular links with congenital fibrosarcoma
Henno S, Loeuillet L, Henry C, D'Hervé D, Azzis O, Ferrer J, Poulain P, Babut JM, Merlio JP, Jouan H, Dubus P
Pathol Res Pract 2003;199(1):35-40
PMID 12650516
Infantile fibrosarcoma of thigh--a case report
Himori K, Hatori M, Watanabe M, Moriya T, Ogose A, Hashimoto H, Kokubun S
Ups J Med Sci 2005;110(1):85-93
PMID 15801689
Secretory carcinoma of the breast: clinicopathologic profile of 14 cases emphasising distant metastatic potential
Hoda RS, Brogi E, Pareja F, Nanjangud G, Murray MP, Weigelt B, Reis-Filho JS, Wen HY
Histopathology 2019 Aug;75(2):213-224
PMID 31012486
TumorFusions: an integrative resource for cancer-associated transcript fusions
Hu X, Wang Q, Tang M, Barthel F, Amin S, Yoshihara K, Lang FM, Martinez-Ledesma E, Lee SH, Zheng S, Verhaak RGW
Nucleic Acids Res 2018 Jan 4;46(D1):D1144-D1149
PMID 29099951
"Secretory" Carcinoma of the Skin Mimicking Secretory Carcinoma of the Breast: Case Report and Literature Review
Huang S, Liu Y, Su J, Liu J, Guo X, Mei F, Zheng J, Liao S
Am J Dermatopathol 2016 Sep;38(9):698-703
PMID 26981741
Mammary analogue secretory carcinoma of salivary glands: a clinicopathologic and molecular study including 2 cases harboring ETV6-X fusion
Ito Y, Ishibashi K, Masaki A, Fujii K, Fujiyoshi Y, Hattori H, Kawakita D, Matsumoto M, Miyabe S, Shimozato K, Nagao T, Inagaki H
Am J Surg Pathol 2015 May;39(5):602-10
PMID 25651470
ETV6-NTRK3 gene fusions and trisomy 11 establish a histogenetic link between mesoblastic nephroma and congenital fibrosarcoma
Knezevich SR, Garnett MJ, Pysher TJ, Beckwith JB, Grundy PE, Sorensen PH
Cancer Res 1998 Nov 15;58(22):5046-8
PMID 9823307
Characterization of a newly identified ETV6-NTRK3 fusion transcript in acute myeloid leukemia
Kralik JM, Kranewitter W, Boesmueller H, Marschon R, Tschurtschenthaler G, Rumpold H, Wiesinger K, Erdel M, Petzer AL, Webersinke G
Diagn Pathol 2011 Mar 15;6:19
PMID 21401966
Inhibiting TRK Proteins in Clinical Cancer Therapy
Lange AM, Lo HW
Cancers (Basel) 2018 Apr 4;10(4)
PMID 29617282
ETV6-NTRK3: a chimeric protein tyrosine kinase with transformation activity in multiple cell lineages
Lannon CL, Sorensen PH
Semin Cancer Biol 2005 Jun;15(3):215-23
PMID 15826836
ETV6-NTRK3 is a common chromosomal rearrangement in radiation-associated thyroid cancer
Leeman-Neill RJ, Kelly LM, Liu P, Brenner AV, Little MP, Bogdanova TI, Evdokimova VN, Hatch M, Zurnadzy LY, Nikiforova MN, Yue NJ, Zhang M, Mabuchi K, Tronko MD, Nikiforov YE
Cancer 2014 Mar 15;120(6):799-807
PMID 24327398
Non-resectable congenital tumors with the ETV6-NTRK3 gene fusion are highly responsive to chemotherapy
McCahon E, Sorensen PH, Davis JH, Rogers PC, Schultz KR
Med Pediatr Oncol 2003 May;40(5):288-92
PMID 12652616
Regression of congenital fibrosarcoma to hemangiomatous remnant with histological and genetic findings
Miura K, Han G, Sano M, Tsutsui Y
Pathol Int 2002 Sep;52(9):612-8
PMID 12406191
Differential diagnosis of congenital fibrosarcoma
Morerio C, Rapella A, Rosanda C, Tassano E, Conte M, Gambini C, Panarello C
Cancer Genet Cytogenet 2004 Jul 15;152(2):167-8
PMID 15262440
Congenital fibrosarcoma with metastasis in a fetus
Nonaka D, Sun CC
Pediatr Dev Pathol 2004 Mar-Apr;7(2):187-91
PMID 15022058
Wilms Tumor and Other Childhood Kidney Tumors Treatment (PDQ): Health Professional Version
PDQ Pediatric Treatment Editorial Board
2020 Jan 9 PDQ Cancer Information Summaries [Internet]
PMID 26389282
Searching for mammary analogue [corrected] secretory carcinoma of salivary gland among its mimics
Pinto A, Nosé V, Rojas C, Fan YS, Gomez-Fernandez C
Mod Pathol 2014 Jan;27(1):30-7
PMID 23807775
ETV6-NTRK3 gene fusion in metastasizing congenital fibrosarcoma
Punnett HH, Tomczak EZ, Pawel BR, de Chadarevian JP, Sorensen PH
Med Pediatr Oncol 2000 Aug;35(2):137-9
PMID 10918240
Cytogenetic and molecular characterization of a congenital mesoblastic nephroma
Ramachandran C, Melnick SJ, Escalon E, Khatib Z, Jhabvala P, Fonseca HB, Smith S, Alamo A, Medina S
Pediatr Dev Pathol 2001 Jul-Aug;4(4):402-11
Retroperitoneal infantile fibrosarcoma: clinical, molecular, and therapeutic aspects of an unusual tumor
Ramphal R, Manson D, Viero S, Zielenska M, Gerstle T, Pappo A
Pediatr Hematol Oncol 2003 Dec;20(8):635-42
PMID 14578034
Targetable kinase gene fusions in high-risk B-ALL: a study from the Children's Oncology Group
Reshmi SC, Harvey RC, Roberts KG, Stonerock E, Smith A, Jenkins H, Chen IM, Valentine M, Liu Y, Li Y, Shao Y, Easton J, Payne-Turner D, Gu Z, Tran TH, Nguyen JV, Devidas M, Dai Y, Heerema NA, Carroll AJ 3rd, Raetz EA, Borowitz MJ, Wood BL, Angiolillo AL, Burke MJ, Salzer WL, Zweidler-McKay PA, Rabin KR, Carroll WL, Zhang J, Loh ML, Mullighan CG, Willman CL, Gastier-Foster JM, Hunger SP
Blood 2017 Jun 22;129(25):3352-3361
PMID 28408464
Congenital fibrosarcoma of the ileum: case report with molecular confirmation and literature review
Rizkalla H, Wildgrove H, Quinn F, Capra M, O'Sullivan MJ
Fetal Pediatr Pathol 2011;30(3):156-60
PMID 21355680
Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia
Roberts KG, Li Y, Payne-Turner D, Harvey RC, Yang YL, Pei D, McCastlain K, Ding L, Lu C, Song G, Ma J, Becksfort J, Rusch M, Chen SC, Easton J, Cheng J, Boggs K, Santiago-Morales N, Iacobucci I, Fulton RS, Wen J, Valentine M, Cheng C, Paugh SW, Devidas M, Chen IM, Reshmi S, Smith A, Hedlund E, Gupta P, Nagahawatte P, Wu G, Chen X, Yergeau D, Vadodaria B, Mulder H, Winick NJ, Larsen EC, Carroll WL, Heerema NA, Carroll AJ, Grayson G, Tasian SK, Moore AS, Keller F, Frei-Jones M, Whitlock JA, Raetz EA, White DL, Hughes TP, Guidry Auvil JM, Smith MA, Marcucci G, Bloomfield CD, Mrózek K, Kohlschmidt J, Stock W, Kornblau SM, Konopleva M, Paietta E, Pui CH, Jeha S, Relling MV, Evans WE, Gerhard DS, Gastier-Foster JM, Mardis E, Wilson RK, Loh ML, Downing JR, Hunger SP, Willman CL, Zhang J, Mullighan CG
N Engl J Med 2014 Sep 11;371(11):1005-15
PMID 25207766
Congenital mesoblastic nephroma t(12;15) is associated with ETV6-NTRK3 gene fusion: cytogenetic and molecular relationship to congenital (infantile) fibrosarcoma
Rubin BP, Chen CJ, Morgan TW, Xiao S, Grier HE, Kozakewich HP, Perez-Atayde AR, Fletcher JA
Am J Pathol 1998 Nov;153(5):1451-8
PMID 9811336
Recurrent R-spondin fusions in colon cancer
Seshagiri S, Stawiski EW, Durinck S, Modrusan Z, Storm EE, Conboy CB, Chaudhuri S, Guan Y, Janakiraman V, Jaiswal BS, Guillory J, Ha C, Dijkgraaf GJ, Stinson J, Gnad F, Huntley MA, Degenhardt JD, Haverty PM, Bourgon R, Wang W, Koeppen H, Gentleman R, Starr TK, Zhang Z, Largaespada DA, Wu TD, de Sauvage FJ
Nature 2012 Aug 30;488(7413):660-4
PMID 22895193
Congenital-infantile fibrosarcoma
Sheng WQ, Hisaoka M, Okamoto S, Tanaka A, Meis-Kindblom JM, Kindblom LG, Ishida T, Nojima T, Hashimoto H
A clinicopathologic study of 10 cases and molecular detection of the ETV6-NTRK3 fusion transcripts using paraffin-embedded tissues Am J Clin Pathol
PMID 11242790
Mammary Analogue Secretory Carcinoma of Salivary Glands: Molecular Analysis of 25 ETV6 Gene Rearranged Tumors With Lack of Detection of Classical ETV6-NTRK3 Fusion Transcript by Standard RT-PCR: Report of 4 Cases Harboring ETV6-X Gene Fusion
Skálová A, Vanecek T, Simpson RH, Laco J, Majewska H, Baneckova M, Steiner P, Michal M
Am J Surg Pathol 2016 Jan;40(1):3-13
PMID 26492182
Newly described salivary gland tumors
Skalova A, Michal M, Simpson RH
Mod Pathol 2017 Jan;30(s1):S27-S43
PMID 28060365
The landscape of kinase fusions in cancer
Stransky N, Cerami E, Schalm S, Kim JL, Lengauer C
Nat Commun 2014 Sep 10;5:4846
PMID 25204415
Anaplastic lymphoma kinase-negative uterine inflammatory myofibroblastic tumor containing the ETV6-NTRK3 fusion gene: a case report
Takahashi A, Kurosawa M, Uemura M, Kitazawa J, Hayashi Y
J Int Med Res 2018 Aug;46(8):3498-3503
PMID 29900760
Expression of the ETV6-NTRK3 gene fusion as a primary event in human secretory breast carcinoma
Tognon C, Knezevich SR, Huntsman D, Roskelley CD, Melnyk N, Mathers JA, Becker L, Carneiro F, MacPherson N, Horsman D, Poremba C, Sorensen PH
Cancer Cell 2002 Nov;2(5):367-76
PMID 12450792
Secretory breast carcinoma: unique, triple-negative carcinoma with a favorable prognosis and characteristic molecular expression
Vasudev P, Onuma K
Arch Pathol Lab Med 2011 Dec;135(12):1606-10
PMID 22129193
Cryptic t(12;15)(p13;q26) producing the ETV6-NTRK3 fusion gene and no loss of IGF2 imprinting in congenital mesoblastic nephroma with trisomy 11: fluorescence in situ hybridization and IGF2 allelic expression analysis
Watanabe N, Kobayashi H, Hirama T, Kikuta A, Koizumi S, Tsuru T, Kaneko Y
Cancer Genet Cytogenet 2002 Jul 1;136(1):10-6
PMID 12165445
Evaluation of a Congenital Infantile Fibrosarcoma by Comprehensive Genomic Profiling Reveals an LMNA-NTRK1 Gene Fusion Responsive to Crizotinib
Wong V, Pavlick D, Brennan T, Yelensky R, Crawford J, Ross JS, Miller VA, Malicki D, Stephens PJ, Ali SM, Ahn H
J Natl Cancer Inst 2015 Nov 12;108(1)
PMID 26563356
The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma
Wu G, Diaz AK, Paugh BS, Rankin SL, Ju B, Li Y, Zhu X, Qu C, Chen X, Zhang J, Easton J, Edmonson M, Ma X, Lu C, Nagahawatte P, Hedlund E, Rusch M, Pounds S, Lin T, Onar-Thomas A, Huether R, Kriwacki R, Parker M, Gupta P, Becksfort J, Wei L, Mulder HL, Boggs K, Vadodaria B, Yergeau D, Russell JC, Ochoa K, Fulton RS, Fulton LL, Jones C, Boop FA, Broniscer A, Wetmore C, Gajjar A, Ding L, Mardis ER, Wilson RK, Taylor MR, Downing JR, Ellison DW, Zhang J, Baker SJ
Nat Genet 2014 May;46(5):444-450
PMID 24705251
ALK, ROS1 and NTRK3 gene rearrangements in inflammatory myofibroblastic tumours
Yamamoto H, Yoshida A, Taguchi K, Kohashi K, Hatanaka Y, Yamashita A, Mori D, Oda Y
Histopathology 2016 Jul;69(1):72-83
PMID 26647767
NTRK3 kinase fusions in Spitz tumours
Yeh I, Tee MK, Botton T, Shain AH, Sparatta AJ, Gagnon A, Vemula SS, Garrido MC, Nakamaru K, Isoyama T, McCalmont TH, LeBoit PE, Bastian BC
J Pathol 2016 Nov;240(3):282-290
PMID 27477320
Jude Children's Research Hospital-Washington University Pediatric Cancer Genome Project
Zhang J, Wu G, Miller CP, Tatevossian RG, Dalton JD, Tang B, Orisme W, Punchihewa C, Parker M, Qaddoumi I, Boop FA, Lu C, Kandoth C, Ding L, Lee R, Huether R, Chen X, Hedlund E, Nagahawatte P, Rusch M, Boggs K, Cheng J, Becksfort J, Ma J, Song G, Li Y, Wei L, Wang J, Shurtleff S, Easton J, Zhao D, Fulton RS, Fulton LL, Dooling DJ, Vadodaria B, Mulder HL, Tang C, Ochoa K, Mullighan CG, Gajjar A, Kriwacki R, Sheer D, Gilbertson RJ, Mardis ER, Wilson RK, Downing JR, Baker SJ, Ellison DW; St
Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas Nat Genet
PMID 23583981


This paper should be referenced as such :
Jean-Loup Huret
t(12;15)(p13;q25) ETV6/NTRK3 in solid tumors
Atlas Genet Cytogenet Oncol Haematol. 2020;24(9):350-356.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Translocations implicated (Data extracted from papers in the Atlas)

 t(12;15)(p13;q25) ETV6/NTRK3

External links

Mitelman database t(12;15)(p13;q25) [CaseList]     t(12;15)(p13;q25) [Transloc - MCList]   ETV6/NTRK3 Fusion - MCList]
COSMIC[ ETV6 ]   [ NTRK3 ]
arrayMap Topo ( C18,C19) arrayMap ((UZH-SIB Zurich)   [auto + random 100 samples .. if exist ]   [tabulated segments]
Disease databaset(12;15)(p13;q25) ETV6/NTRK3 in solid tumors
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Mon Dec 14 18:30:51 CET 2020

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us