Αρχική World News Patients with Early Stage NSCLC Have a Higher TMB in Comparison to...

Patients with Early Stage NSCLC Have a Higher TMB in Comparison to Advanced Stage Disease

The tumours of patients with stage I and II early non-small cell lung cancer (NSCLC) demonstrate the highest tumour mutational burden (TMB) and most often display the mutational signature associated with tobacco smoking, according to findings presented at the MAP 2020 Virtual Congress.

Guus Van den Heuvel, Pulmonology, Radboud University Medical Center Nijmegen, Netherlands remarked that recent studies demonstrate varying therapeutic effects of immune checkpoint inhibitors in patients with NSCLC and high TMB, prompting this study that examined the link between high TMB in a large series of clinical NSCLC samples irrespective of tumour stage. Van den Heuvel and colleagues also aimed to identify the particular mutational processes involved by assessing mutational signatures.

In this retrospective observational descriptive study, the investigators extracted DNA from cytological samples and formalin-fixed, paraffin-embedded tissue sections of tumour samples obtained from patients with stages I, II, III, and IV of NSCLC. DNA sequencing was performed using the TruSight™ Oncology 500 panel comprising 523 cancer-related genes. TMB was defined as the number of somatic mutations per megabase (mut/Mb) in each sample. Tumour samples containing a minimum of 30 somatic variants were utilised for mutational signature profiling.

The highest TMB was detected in stage I and II tumours

Sequencing was performed on 197 samples. The median non-synonymous TMB was determined to be 8.7 mut/Mb (range, 0 to 85.4).

Compared with this median, stage I and II tumours had TMB of 67% and the TMB in stage III and IV tumours was 47.5% (p = 0.01).

Evaluation of mutational signatures was done in 76 (39%) tumour samples with median TMB of 15.2 mut/Mb. The single base substitution (SBS) signature 4, which is associated with tobacco smoking, was present in 34 of 76 (45%) samples. The SBS4 signature was significantly more present in early stages I and II disease compared with advanced stages III and IV (p = 0.003).

The signatures SBS2 and SBS13, which are associated with activity of the AID/APOBEC family of DNA deaminases and may be linked to cancer development, were observed in 30 of 76 (39%) samples.

One tumour with TMB 26 mut/Mb also harboured SBS7a and SBS7b signatures that are associated with UV light exposure.

Conclusions

The authors concluded that, in general, patients with early stage NSCLC have a higher TMB in comparison to advanced stages and more often show a SBS4 signature, which is associated with tobacco smoking.

They further advise that these findings may have clinical implications for a subpopulation of patients that may benefit from adjuvant immuno-oncology.

No external funding was disclosed for this study.

Kevin Litchfield of the Francis Crick Institute in London, UK, who discussed the study results said that mutational signature data as a window into disease epidemiology and clinical characteristics is a novel promising research approach. From the interpretation point this study opens several questions such as are smokers more likely to be admitted with breathlessness or exacerbations of COPD and diagnosed at earlier stage; are primary care physicians more aware of lung cancer risk and therefore, more likely to organise X-rays and diagnose early; and in terms of technical considerations, it is important to look into correction for multiplicity, clonality of mutations, other signatures.

Reference

3MO – Van den Heuvel G, De Voer R, Kroeze L, Van den Heuvel MM, et al. Mutational signatures in the perspective of tumour mutational burden in patients with non-small-cell lung cancer. MAP 2020 Virtual Congress (9-10 October 2020).

Source

NEWSLETTER

Συμπληρώστε το email σας για να λαμβάνετε τις σημαντικότερες ειδήσεις από το ogkologos.com

Βρείτε μας

2,449ΥποστηρικτέςΚάντε Like
57ΑκόλουθοιΑκολουθήστε

Διαβαστε Επίσης

Καρκίνος και Κορωνοϊός (COVID-19) ΜΕΡΟΣ Α

Εάν είστε καρκινοπαθής, το ανοσοποιητικό σας σύστημα μπορεί να μην είναι τόσο ισχυρό όσο κανονικά, έτσι μπορεί να ανησυχείτε για τους κινδύνους που σχετίζονται...

ΠΑΓΚΟΣΜΙΑ ΗΜΕΡΑ ΚΑΡΚΙΝΟΥ

Η Παγκόσμια Ημέρα Κατά του Καρκίνου καθιερώθηκε με πρωτοβουλία της Διεθνούς Ένωσης κατά του Καρκίνου (UICC), που εκπροσωπεί 800 οργανώσεις σε 155 χώρες του...

ΕΞΕΛΙΞΕΙΣ ΣΤΗ ΘΕΡΑΠΕΙΑ ΤΟΥ ΜΗ-ΜΙΚΡΟΚΥΤΤΑΡΙΚΟΥ ΚΑΡΚΙΝΟΥ ΤΟΥ ΠΝΕΥΜΟΝΑ (ΜΜΚΠ)

ΕΞΕΛΙΞΕΙΣ ΣΤΗ ΘΕΡΑΠΕΙΑ ΤΟΥ ΜΗ-ΜΙΚΡΟΚΥΤΤΑΡΙΚΟΥ ΚΑΡΚΙΝΟΥ ΤΟΥ ΠΝΕΥΜΟΝΑ (ΜΜΚΠ) Γράφει ο Δρ Παπαδούρης Σάββας, Παθόλογος-Ογκολόγος   Ο ΜΜΚΠ βρίσκεται αναλογικά στο 80% και πλέον του συνολικού...

Διατρέχουν όντως οι καρκινοπαθείς μεγαλύτερο κίνδυνο λόγω κοροναϊού;

Σε πρακτικό επίπεδο, τα δεδομένα των σχετικών μελετών υποδηλώνουν ότι η χημειοθεραπεία ή οι άλλες αντι-νεοπλασματικές θεραπείες δεν αυξάνουν σημαντικά τον κίνδυνο θνησιμότητας από...

FDA: Η ακτινοβολία των smartphones δεν προκαλεί καρκίνο

Σε μια νέα έκθεσή της, η Υπηρεσία Τροφίμων και Φαρμάκων (FDA) των ΗΠΑ αναφέρει ότι επανεξέτασε τις σχετικές επιστημονικές έρευνες που δημοσιεύθηκαν τα τελευταία...

Νέα ανακάλυψη, νέα ελπίδα για τον καρκίνο

Ένα νεοανακαλυφθέν τμήμα του ανοσοποιητικού μας συστήματος θα μπορούσε να αξιοποιηθεί για την αντιμετώπιση όλων των ειδών καρκίνου, σύμφωνα με επιστήμονες του πανεπιστημίου Cardiff...
- Advertisment -

Ροή Ειδήσεων

Overall Breast Cancer Incidence Down Since 1999, Rates Increase for Women Under 40

U.S. breast cancer death rates decreased by about 1% per year between 2013 and 2018. What were the new case rates during that same...

Impressive Responses to PD-1 Blockade in a Large Cohort of Children and Young Adults with Recurrent/Progressive Germline DNA Replication Repair-Deficient Cancers

A large, observational, registry-based study that leveraged systematically collected data gathered both retrospectively and prospectively through the International Replication Repair Deficiency Consortium reveals impressive...

2-Year-Boy Is So Excited To See Himself In Disney’s ‘Encanto’

The importance of representation in media has been a growing topic of concern, and companies have responded by adding more diversity to their characters,...

Man Walks Entire Continent To Spread Awareness About Mental Health & Suicide Prevention

Matthew Fennell is walking over 3,000 miles across Australia for an important cause and one that is near and dear to his heart. Last year,...

Boy Battling Cancer Becomes Honorary Police Officer, Sworn In To 45 Agencies

At just ten years old, Devarjaye “DJ” Daniel has already been through more than most people go through in their entire lives. DJ has been...

Paclitaxel and Carboplatin Not Inferior When Compared with Paclitaxel and Ifosfamide for the Treatment of Patients with Uterine Carcinosarcoma

With regard to overall survival (OS), paclitaxel and carboplatin was not inferior and demonstrated improved progression-free survival (PFS) when compared with paclitaxel and ifosfamide...