Prevalence of heterozygous and homozygous 9p21 deletions in human cancer: a tissue microarray study on 4,999 tumors from 125 different tumor types

Our plain-English summary of Prevalence of heterozygous and homozygous 9p21 deletions in human cancer: a tissue microarray study on 4,999 tumors from 125 different tumor types, by N. Gorbokon, K. Teljuk, N. Schraps, et al (Molecular Medicine, 2026).

The study

• Authors: N. Gorbokon, K. Teljuk, N. Schraps, M. Lennartz, S.D. Rico, S. Kind, V. Reiswich, F. Viehweger, F. Lutz, C. Fraune, A.M. Luebke, A. Menz, R. Schlichter, T. Krech, A. Hinsch, E. Burandt, G. Sauter, R. Simon, S. Steurer, A.H. Marx, P. Lebok, D. Dum, S. Minner, F. Jacobsen, T.S. Clauditz, T. Hackert, F.G. Uzunoglu, C. Bernreuther, M. Kluth
• Journal: Molecular Medicine
• Published: 2026;32(1)
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Homozygous 9p21 deletions are the major cause for MTAP deficiency, making cancer cells more vulnerable towards drugs targeting various pathways. This study aimed to assess the prevalence of heterozygous and homozygous 9p21 deletions in cancer.

Methods: A tissue microarray containing 7,172 samples from 125 different tumor entities was analyzed by fluorescence in situ hybridization. This method allows the detection of deletions within single tumor cells, while admixted non-neoplastic cells are omitted. Consecutive sections were immunostained for MTAP and p16 (CDKN2A).

Results: Among 4,999 evaluable tumors, 10.7% had heterozygous and 7.4% homozygous deletions, which occurred in different tumor categories. Homozygous deletions were most frequent in mesothelioma (up to 47.8%), pancreatic ductal adenocarcinoma (44.7%), and urothelial carcinoma (up to 36.4%) while heterozygous deletions predominated in squamous cell carcinoma (up to 34.3%), leiomyosarcoma (31.4%), and esophageal adenocarcinoma (30.8%). The proportion of homozygous 9p21 deletions was high in mesothelioma (up to 91.6%), urothelial carcinoma (up to 80.0%), and pancreatic ductal adenocarcinoma (76.4%), intermediate in squamous cell carcinomas of different organs (12.5-50.0%) and pulmonary adenocarcinoma (46.3%), and low in endometrioid (9.1%) and high-grade serous (4.0%) ovarian carcinoma. MTAP and p16 immunostaining was absent in homozygous 9p21 deletions, while heterozygously deleted cancers showed markedly decreased MTAP immunostaining (p < 0.0001), with unchanged p16 staining.

Conclusions: These data provide a comprehensive overview on the prevalence on homozygous and heterozygous 9p21 deletions in cancer and demonstrate that different cancer types markedly differ in their ratio of homozygous/heterozygous 9p21 deletions. The strong concordance between homozygous 9p21 deletions and absent MTAP immunostaining highlights the effectiveness of immunohistochemistry in detecting MTAP deficiency.

© 2026. The Author(s).

In plain English

This laboratory study looked at 9p21 deletions, a genetic change that can remove the MTAP and CDKN2A (p16) genes, across many cancer types. It did not study asbestos or any other exposure. The authors tested archived tumor samples from three German pathology departments using a fluorescence test (FISH). Of 7,172 samples, 4,999 could be interpreted. Overall, 10.7% of tumors had lost one copy of 9p21 (heterozygous deletion) and 7.4% had lost both copies (homozygous deletion). Homozygous deletions were most frequent in mesothelioma (up to 47.8%), ductal adenocarcinoma of the pancreas (44.7%) and urothelial carcinoma (up to 36.4%). Among mesotheliomas with a deletion, up to 91.6% were homozygous. MTAP staining was absent in all 304 homozygously deleted tumors with MTAP results, and p16 staining in all 369 with p16 results. Tumors with a one-copy deletion had markedly lower MTAP staining than tumors without a deletion. The authors concluded that cancer types differ markedly in their mix of deletion types, and that MTAP staining is supported as the gold standard method for detecting MTAP deficiency. They named the still low number of cases as the main limitation.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory tissue microarray study. Archived tumor samples were tested for 9p21 deletions by fluorescence in situ hybridization (FISH), and consecutive sections were stained (immunohistochemistry) for MTAP and p16.
• Who was studied: 7,172 primary tumor samples from 125 tumor types and subtypes, taken from pathology archives in Hamburg, Osnabrueck and Fuerth, Germany. Of these, 4,999 samples (69.7%) could be interpreted by FISH.
• Exposure: No asbestos or other environmental or occupational exposure was studied. The study measured a genetic change (9p21 deletion of one copy or both copies) and MTAP and p16 protein staining in tumors.
• Main results:
  • Among all 4,999 evaluable tumors, 10.7% had a heterozygous (one-copy) 9p21 deletion and 7.4% had a homozygous (both-copy) deletion.
  • At least one tumor with a 9p21 deletion was found in 84 of the 125 tumor types.
  • Homozygous 9p21 deletions were most frequent in mesothelioma (up to 47.8%).
  • Homozygous deletions were also frequent in ductal adenocarcinoma of the pancreas (44.7%), urothelial carcinoma (up to 36.4%) and adenocarcinoma of the papilla of Vater (34.8%).
  • Heterozygous deletions were most frequent in squamous cell carcinoma (up to 34.3%), leiomyosarcoma (31.4%), esophageal adenocarcinomas (30.8%) and malignant melanoma (29.4%).
  • Among tumors with a 9p21 deletion, the share that were homozygous was high in mesothelioma (up to 91.6%), urothelial carcinoma (up to 80.0%), pancreatic ductal adenocarcinoma (76.4%) and mucinous carcinoma of the ovary (66.7%).
  • Among tumors with a 9p21 deletion, the share that were homozygous was low in endometrioid (9.1%) and serous (4.0%) carcinoma of the ovary.
  • All 304 tumors with a homozygous 9p21 deletion and MTAP results showed complete loss of MTAP staining.
  • p16 staining was not detectable in any of the 369 tumors with a homozygous 9p21 deletion and p16 results.
  • MTAP staining was markedly lower in 468 heterozygously deleted cancers than in 3,554 cancers without a deletion (p less than 0.0001).
  • Average p16 staining was slightly higher in 531 heterozygously deleted cancers than in 3,899 cancers without a deletion. The difference was not statistically significant (p = 0.4564).
  • Of 415 MTAP-deficient cases, 26.7% did not have a homozygous deletion: 21.4% had a normal 9p21 status and 5.3% had a heterozygous deletion.
  • Of 3,705 p16-negative cases, 90.0% did not have a homozygous deletion: 79.5% had a normal 9p21 status and 10.5% had a heterozygous deletion.
• The authors' conclusion: The authors concluded that the proportions of heterozygous and homozygous 9p21 (MTAP) deletions vary markedly between tumor types. They also concluded that the near perfect concordance between homozygous deletions and absent MTAP staining further supports immunohistochemistry as the gold standard method for detecting MTAP deficiency.
• Limitations the authors state:
  • The authors called the still low number of cases the main limitation.
  • The FISH method cannot detect exon deletions.
  • Manual grading of staining intensity is semiquantitative.
  • The tumor collection was artificially composed and overrepresented less frequent cancer types, so the overall rates may not reflect the general cancer population.

Topics

Medical terms in this study, explained in our Lexicon: MTAP, Fluorescence In Situ Hybridization (FISH), CDKN2A, Homozygous Deletion, Mesothelioma, Adenocarcinoma, Carcinoma, Squamous Cell Carcinoma.

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