HSP110 T17 simplifies and improves the microsatellite instability testing in patients with colorectal cancer
Olivier Buhard
(1)
,
Anaïs Lagrange
(1)
,
Agathe Guilloux
(1, 2)
,
Chrystelle Colas
(1)
,
Mouna Chouchène
(1)
,
Kristell Wanherdrick
(1)
,
Florence Coulet
(1)
,
Erell Guillerm
(1)
,
Coralie Dorard
(1)
,
Laetitia Marisa
(1)
,
Adem Bokhari
(1)
,
Malorie Greene
(1)
,
Nizar El-Murr
(1)
,
Sahra Bodo
(1)
,
Martine Muleris
(1)
,
Isabelle Sourouille
(1)
,
Magali Svrcek
(3, 1)
,
Pascale Cervera
(4, 5, 3)
,
Hélène Blanché
(5)
,
Jérémie H Lefevre
(1, 6)
,
Yann Parc
(1, 6)
,
Come Lepage
(7, 5)
,
Caroline Chapusot
(5, 7)
,
Anne-Marie Bouvier
(5, 7)
,
Carmen Garrido
(8, 7)
,
Marie-Pierre Gaub
(9)
,
Janick Selves
(10)
,
Kerryn Garrett
,
Barry Iacopetta
(11)
,
Richie Soong
(12)
,
Richard Hamelin
(1)
,
Olivier Lascols
(13, 5, 4)
,
Thierry André
(1, 5)
,
Jean-François Fléjou
(1, 3)
,
Ada Collura
(1)
,
Alex Duval
(1)
1
UMRS893 -
Centre de Recherche Saint-Antoine
2 X - École polytechnique
3 CIT - (le programme) Cartes d'identité des tumeurs
4 UPMC - Université Pierre et Marie Curie - Paris 6
5 CHU Saint-Antoine [AP-HP]
6 Fondation Jean Dausset CEPH
7 Registre Bourguignon des Cancers Digestifs
8 NUS - National University of Singapore
9 LNC - Lipides - Nutrition - Cancer (U866)
10 Développement et physiopathologie de l'intestin et du pancréas
11 St John God HealthCare
12 UWA - The University of Western Australia
13 UNICANCER/CRLCC-CGFL - Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon]
2 X - École polytechnique
3 CIT - (le programme) Cartes d'identité des tumeurs
4 UPMC - Université Pierre et Marie Curie - Paris 6
5 CHU Saint-Antoine [AP-HP]
6 Fondation Jean Dausset CEPH
7 Registre Bourguignon des Cancers Digestifs
8 NUS - National University of Singapore
9 LNC - Lipides - Nutrition - Cancer (U866)
10 Développement et physiopathologie de l'intestin et du pancréas
11 St John God HealthCare
12 UWA - The University of Western Australia
13 UNICANCER/CRLCC-CGFL - Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon]
Agathe Guilloux
- Fonction : Auteur
- PersonId : 1218431
- IdHAL : agathe-guilloux
- ORCID : 0000-0003-0473-1970
Florence Coulet
- Fonction : Auteur
- PersonId : 758768
- ORCID : 0000-0002-5325-5272
Martine Muleris
- Fonction : Auteur
- PersonId : 740173
- IdHAL : martine-muleris
- ORCID : 0000-0002-6009-5529
- IdRef : 070382506
Pascale Cervera
- Fonction : Auteur
- PersonId : 766366
- ORCID : 0000-0001-6048-2214
Hélène Blanché
- Fonction : Auteur
- PersonId : 766613
- ORCID : 0000-0003-2115-575X
Anne-Marie Bouvier
- Fonction : Auteur
- PersonId : 906758
Kerryn Garrett
- Fonction : Auteur
Thierry André
- Fonction : Auteur
- PersonId : 761084
- ORCID : 0000-0002-7718-2645
Résumé
Background Every colorectal cancer (CRC) patient should be tested for microsatellite instability (MSI, a marker for defective DNA mismatch repair) as a first screen for Lynch syndrome (LS). In this study, we investigated whether it may be possible to improve the detection of MSI in CRC. We examined whether the HT17 DNA repeat (critical for correct splicing of the chaperone HSP110) might constitute a superior marker for diagnosis of the MSI phenotype in patients with CRC compared with the standard panel of markers (pentaplex).Methods The HT17 polymorphism was analysed in germline DNA from 1037 multi-ethnic individuals. We assessed its sensitivity and specificity for detecting MSI in a multicentre, population-based cohort of 685 patients with CRC and an additional series of 70 patients with CRC considered to be at-risk of LS. All cases were screened earlier for MSI using pentaplex markers. Cases showing discordant HT17/pentaplex results were further examined for the expression of mismatch repair proteins.Results HT17 status was analysed independently and blinded to previous results from pentaplex genotyping. HT17 showed no germline allelic variation outside a very narrow range. Compared with the pentaplex panel, HT17 showed better sensitivity (0.984 (95% CI 0.968 to 0.995) vs 0.951 (95% CI 0.925 to 0.972)) and similar specificity (0.997 (95% CI 0.989 to 1.000) for both) for the detection of MSI. Furthermore, HT17 alone correctly classified samples judged to be uncertain with the pentaplex panel and showed excellent ability to detect MSI in patients with LS.Conclusions HT17 simplifies and improves the current standard molecular methods for detecting MSI in CRC.