Skip to main content
SpringerLink
Log in

ATM mutation in aggressive uterine adenosarcoma in which systemic chemotherapies had remarkable effects

  • Case Report
  • Published:
International Cancer Conference Journal Aims and scope Submit manuscript

Abstract

Uterine adenosarcoma is a rare gynecologic malignancy, and 10–25% of the cases exhibit clinically aggressive behaviors. Although TP53 mutations are frequently identified in high-grade adenosarcomas of the uterus, definitive gene alterations have not been identified in uterine adenosarcomas. Specifically, no reports have described mutations in homologous recombination deficiency-related genes in uterine adenosarcomas. This study presents a case of uterine adenosarcoma without sarcomatous overgrowth but with TP53 mutation that exhibited clinically aggressive behaviors. The patient had an ATM mutation, which is a gene associated with homologous recombination deficiency, and exhibited a good response against platinum-based chemotherapy and possible therapeutic target by poly(ADP-ribose) polymerase inhibitors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Carroll A, Ramirez PT, Westin SN, Soliman PT, Munsell MF, Nick AM, Schmeler KM, Klopp AH, Fleming ND (2014) Uterine adenosarcoma: an analysis on management, outcomes, and risk factors for recurrence. Gynecol Oncol 135(3):455–461. https://doi.org/10.1016/j.ygyno.2014.10.022

    Article  PubMed  PubMed Central  Google Scholar 

  2. Ulrich UA, Denschlag D (2018) Uterine Adenosarcoma. Oncol Res Treat 41(11):693–696. https://doi.org/10.1159/000494067

    Article  PubMed  Google Scholar 

  3. Clement PB, Scully RE (1990) Mullerian adenosarcoma of the uterus: a clinicopathologic analysis of 100 cases with a review of the literature. Hum Pathol 21(4):363–381. https://doi.org/10.1016/0046-8177(90)90198-e

    Article  CAS  PubMed  Google Scholar 

  4. Eichhorn JH, Young RH, Clement PB, Scully RE (2002) Mesodermal (müllerian) adenosarcoma of the ovary: a clinicopathologic analysis of 40 cases and a review of the literature. Am J Surg Pathol 26(10):1243–1258. https://doi.org/10.1097/00000478-200210000-00001

    Article  PubMed  Google Scholar 

  5. Choi J, Manzano A, Dong W, Bellone S, Bonazzoli E, Zammataro L, Yao X, Deshpande A, Zaidi S, Guglielmi A, Gnutti B, Nagarkatti N, Tymon-Rosario JR, Harold J, Mauricio D, Zeybek B, Menderes G, Altwerger G, Jeong K, Zhao S, Buza N, Hui P, Ravaggi A, Bignotti E, Romani C, Todeschini P, Zanotti L, Odicino F, Pecorelli S, Ardighieri L, Bilguvar K, Quick CM, Silasi DA, Huang GS, Andikyan V, Clark M, Ratner E, Azodi M, Imielinski M, Schwartz PE, Alexandrov LB, Lifton RP, Schlessinger J, Santin AD (2021) Integrated mutational landscape analysis of uterine leiomyosarcomas. Proc Natl Acad Sci USA. https://doi.org/10.1073/pnas.2025182118

    Article  PubMed  PubMed Central  Google Scholar 

  6. Ngoi NYL, Tan DSP (2021) The role of homologous recombination deficiency testing in ovarian cancer and its clinical implications: do we need it? ESMO Open 6(3):100144. https://doi.org/10.1016/j.esmoop.2021.100144

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Takamatsu S, Brown JB, Yamaguchi K, Hamanishi J, Yamanoi K, Takaya H, Kaneyasu T, Mori S, Mandai M, Matsumura N (2022) Utility of homologous recombination deficiency biomarkers across cancer types. JCO Precis Oncol 6:e2200085. https://doi.org/10.1200/PO.22.00085

    Article  PubMed  PubMed Central  Google Scholar 

  8. Mekonnen N, Yang H, Shin YK (2022) Homologous recombination deficiency in ovarian, breast, colorectal, pancreatic, non-small cell lung and prostate cancers, and the mechanisms of resistance to PARP inhibitors. Front Oncol 12:880643. https://doi.org/10.3389/fonc.2022.880643

    Article  PubMed  PubMed Central  Google Scholar 

  9. Ciccarone F, Bruno M, De Paolis E, Piermattei A, De Bonis M, Lorusso D, Zannoni GF, Normanno N, Minucci A, Scambia G, Ferrandina G (2022) Role of homologous recombination repair (HRR) genes in uterine leiomyosarcomas: a retrospective analysis. Cancers 14(8):1934. https://doi.org/10.3390/cancers14081934

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Dall GV, Hamilton A, Ratnayake G, Scott C, Barker H (2022) Interrogating the genomic landscape of uterine leiomyosarcoma: a potential for patient benefit. Cancers 14(6):1561. https://doi.org/10.3390/cancers14061561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Gannon HS, Woda BA, Jones SN (2012) ATM phosphorylation of Mdm2 Ser394 regulates the amplitude and duration of the DNA damage response in mice. Cancer Cell 21(5):668–679. https://doi.org/10.1016/j.ccr.2012.04.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Nacev BA, Sanchez-Vega F, Smith SA, Antonescu CR, Rosenbaum E, Shi H, Tang C, Socci ND, Rana S, Gularte-Mérida R, Zehir A, Gounder MM, Bowler TG, Luthra A, Jadeja B, Okada A, Strong JA, Stoller J, Chan JE, Chi P, D’Angelo SP, Dickson MA, Kelly CM, Keohan ML, Movva S, Thornton K, Meyers PA, Wexler LH, Slotkin EK, Glade Bender JL, Shukla NN, Hensley ML, Healey JH, La Quaglia MP, Alektiar KM, Crago AM, Yoon SS, Untch BR, Chiang S, Agaram NP, Hameed MR, Berger MF, Solit DB, Schultz N, Ladanyi M, Singer S, Tap WD (2022) Clinical sequencing of soft tissue and bone sarcomas delineates diverse genomic landscapes and potential therapeutic targets. Nat Commun 13(1):3405. https://doi.org/10.1038/s41467-022-30453-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Piscuoglio S, Burke KA, Ng CK, Papanastasiou AD, Geyer FC, Macedo GS, Martelotto LG, de Bruijn I, De Filippo MR, Schultheis AM, Ioris RA, Levine DA, Soslow RA, Rubin BP, Reis-Filho JS, Weigelt B (2016) Uterine adenosarcomas are mesenchymal neoplasms. J Pathol 238(3):381–388. https://doi.org/10.1002/path.4675

    Article  CAS  PubMed  Google Scholar 

  14. Bean GR, Anderson J, Sangoi AR, Krings G, Garg K (2019) DICER1 mutations are frequent in müllerian adenosarcomas and are independent of rhabdomyosarcomatous differentiation. Mod Pathol 32(2):280–289. https://doi.org/10.1038/s41379-018-0132-5

    Article  PubMed  Google Scholar 

  15. Ok Atılgan A, Yılmaz Akçay E, Özen Ö, Haberal Reyhan AN, Ayhan A (2022) The overexpression of programmed death-ligand 2 in uterine adenosarcoma: correlation with high-grade morphology, mutant type TP53 expression and clinical outcomes. Int J Surg Pathol. https://doi.org/10.1177/10668969221095189

    Article  PubMed  Google Scholar 

  16. da Costa LT, Dos Anjos LG, Kagohara LT, Torrezan GT, De Paula CAA, Baracat EC, Carraro DM, Carvalho KC (2021) The mutational repertoire of uterine sarcomas and carcinosarcomas in a Brazilian cohort: a preliminary study. Clinics 76:e2324. https://doi.org/10.6061/clinics/2021/e2324

    Article  PubMed  PubMed Central  Google Scholar 

  17. Hodgson A, Amemiya Y, Seth A, Djordjevic B, Parra-Herran C (2017) High-grade Müllerian adenosarcoma: genomic and clinicopathologic characterization of a distinct neoplasm with prevalent TP53 pathway alterations and aggressive behavior. Am J Surg Pathol 41(11):1513–1522. https://doi.org/10.1097/PAS.0000000000000907

    Article  PubMed  Google Scholar 

  18. Howitt BE, Sholl LM, Dal Cin P, Jia Y, Yuan L, MacConaill L, Lindeman N, Kuo F, Garcia E, Nucci MR, Quade BJ (2015) Targeted genomic analysis of Müllerian adenosarcoma. J Pathol 235(1):37–49. https://doi.org/10.1002/path.4442

    Article  CAS  PubMed  Google Scholar 

  19. Seligson ND, Kautto EA, Passen EN, Stets C, Toland AE, Millis SZ, Meyer CF, Hays JL, Chen JL (2019) Functional loss defines a targetable subset in Leiomyosarcoma. Oncologist 24(7):973–979. https://doi.org/10.1634/theoncologist.2018-0448

    Article  CAS  PubMed  Google Scholar 

  20. Lee PJ, Yoo NS, Hagemann IS, Pfeifer JD, Cottrell CE, Abel HJ, Duncavage EJ (2017) Spectrum of mutations in leiomyosarcomas identified by clinical targeted next-generation sequencing. Exp Mol Pathol 102(1):156–161. https://doi.org/10.1016/j.yexmp.2017.01.012

    Article  CAS  PubMed  Google Scholar 

  21. Fan L, Fei X, Zhu Y, Chi C, Pan J, Sha J, Xin Z, Gong Y, Du X, Wang Y, Dong B, Xue W (2021) Distinct response to platinum-based chemotherapy among patients with metastatic castration-resistant prostate cancer harboring alterations in genes involved in homologous recombination. J Urol 206(3):630–637. https://doi.org/10.1097/JU.0000000000001819

    Article  PubMed  Google Scholar 

  22. Pennington KP, Walsh T, Harrell MI, Lee MK, Pennil CC, Rendi MH, Thornton A, Norquist BM, Casadei S, Nord AS, Agnew KJ, Pritchard CC, Scroggins S, Garcia RL, King MC, Swisher EM (2014) Germline and somatic mutations in homologous recombination genes predict platinum response and survival in ovarian, fallopian tube, and peritoneal carcinomas. Clin Cancer Res 20(3):764–775. https://doi.org/10.1158/1078-0432.CCR-13-2287

    Article  CAS  PubMed  Google Scholar 

  23. Frimer M, Levano KS, Rodriguez-Gabin A, Wang Y, Goldberg GL, Horwitz SB, Hou JY (2016) Germline mutations of the DNA repair pathways in uterine serous carcinoma. Gynecol Oncol 141(1):101–107. https://doi.org/10.1016/j.ygyno.2015.12.034

    Article  CAS  PubMed  Google Scholar 

  24. Choi M, Kipps T, Kurzrock R (2016) ATM mutations in cancer: therapeutic implications. Mol Cancer Ther 15(8):1781–1791. https://doi.org/10.1158/1535-7163.MCT-15-0945

    Article  CAS  PubMed  Google Scholar 

  25. Penson RT, Valencia RV, Cibula D, Colombo N, Leath CA, Bidziński M, Kim JW, Nam JH, Madry R, Hernández C, Mora PAR, Ryu SY, Milenkova T, Lowe ES, Barker L, Scambia G (2020) Olaparib versus nonplatinum chemotherapy in patients with platinum-sensitive relapsed ovarian cancer and a germline BRCA1/2 mutation (SOLO3): a randomized phase III trial. J Clin Oncol 38(11):1164–1174. https://doi.org/10.1200/JCO.19.02745

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Kristeleit R, Lisyanskaya A, Fedenko A, Dvorkin M, de Melo AC, Shparyk Y, Rakhmatullina I, Bondarenko I, Colombo N, Svintsitskiy V, Biela L, Nechaeva M, Lorusso D, Scambia G, Cibula D, Póka R, Oaknin A, Safra T, Mackowiak-Matejczyk B, Ma L, Thomas D, Lin KK, McLachlan K, Goble S, Oza AM (2022) Rucaparib versus standard-of-care chemotherapy in patients with relapsed ovarian cancer and a deleterious BRCA1 or BRCA2 mutation (ARIEL4): an international, open-label, randomised, phase 3 trial. Lancet Oncol 23(4):465–478. https://doi.org/10.1016/S1470-2045(22)00122-X

    Article  CAS  PubMed  Google Scholar 

  27. Fedier A, Schlamminger M, Schwarz VA, Haller U, Howell SB, Fink D (2003) Loss of atm sensitises p53-deficient cells to topoisomerase poisons and antimetabolites. Ann Oncol 14(6):938–945. https://doi.org/10.1093/annonc/mdg240

    Article  CAS  PubMed  Google Scholar 

  28. Cheng Q, Chen L, Li Z, Lane WS, Chen J (2009) ATM activates p53 by regulating MDM2 oligomerization and E3 processivity. EMBO J 28(24):3857–3867. https://doi.org/10.1038/emboj.2009.294

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, 54 Shogoin, Kawahara-Cho, Sakyo-Ku, Kyoto, 606-8507, Japan

    Misaki Koyama, Ken Yamaguchi, Yoshitsugu Chigusa, Koji Yamanoi, Mana Taki, Masumi Sunada, Akihito Horie, Junzo Hamanishi & Masaki Mandai

  2. Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan

    Sachiko Minamiguchi

Authors
  1. Misaki Koyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ken Yamaguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yoshitsugu Chigusa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Koji Yamanoi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mana Taki
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Masumi Sunada
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Akihito Horie
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Junzo Hamanishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Sachiko Minamiguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Masaki Mandai
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ken Yamaguchi.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Research involving human participants and/or animals

This article does not contain any studies with animals performed by any of the authors.

Informed consent

Informed consent was obtained from the patient for whom identifying information is included in this article.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Koyama, M., Yamaguchi, K., Chigusa, Y. et al. ATM mutation in aggressive uterine adenosarcoma in which systemic chemotherapies had remarkable effects. Int Canc Conf J 12, 120–125 (2023). https://doi.org/10.1007/s13691-022-00591-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13691-022-00591-6

Keywords

Search

Navigation